Handbook of Oxidative Stress in Cancer: Therapeutic Aspects

Preface
Contents
About the Editor
Contributors
Part I: Therapeutic Implications of Natural Compounds
1 Elimination of Senescent Cells by Polyphenols and Flavonoids
Introduction
Cellular Senescence
Markers of Cellular Senescence
Senescence-Associated Mitochondrial Dysfunction (SAMD)
Senescence-Associated Secretory Phenotype (SASP)
Bystander Effect
Therapy-Induced Senescence (TIS)
TIS Induced by Polyphenols
Escape From TIS
Senescent Cells: A Survival Niche Generating a Complex Tumor Environment
Importance of TIS by the Example of Radiotherapy-Induced Senescence
Role of TIS in Other Cancer Treatments
Polyphenols Inhibiting SASP (Senostatics)
Apigenin
Epigallocatechin-3-Gallate (EGCG)
Resveratrol
Quercetin
Polyphenols as Senolytics (Polyphenols Killing Senescent Cells)
Fisetin
Quercetin
Epigallocatechin-3-Gallate (EGCG)
Curcumin
Herbal Extracts with Senolytic and Senomorphic Properties
Extract of the Plant Solidago virgaurea Subsp. alpestris
Alcoholic Extract of Ajuga taiwanensis
Pinellia ternata Tuber
Olive Plant
Conclusion
References
2 Natural Dietary Alkaloids and Its Synthetic Derivatives as Oxidative Stress-Inducing Agents for Cancer Therapy
Introduction
Berberine
Piperine
Neferine
Piperlongumine
Conclusion
References
3 Natural Therapeutic Strategies for Modulating Oxidative Stress in Cancer
Introduction
Oxidative Stress and Carcinogenesis
Antioxidant Defense Mechanism
Oxidative Stress and Natural Compounds
The Role of Antioxidant Potential of Phytochemicals in Oxidative Stress
Mechanism of Natural Compounds in Combination with Chemotherapy
Marine Product with Antioxidative Stress Activity
Microbial Antioxidative Stress Compounds
Conclusion
Future Perspective
References
4 Antioxidant in Cancer
Introduction
Reactive Oxygen Species (ROS)
Reactive Oxygen Species (ROS) in Cancer
Antioxidants
Antioxidants Types
Defense Mechanism of Antioxidant
Antioxidant: Preventer of Cancer
Antioxidant: Promoter of Cancer
Antioxidant: An Achilles´ Heel
The Antioxidant Conundrum: Friend or Foe
Conclusion
References
5 Antioxidant Activity of Phytochemicals in Cancer
Introduction
Role of Reactive Oxygen Species (ROS) in Cancer Progression
ROS and Chemoresistance Development
Cellular Redox System and Molecular Mechanisms Against ROS
Phytochemicals and Their Antioxidant Activity in Cancer
Triphala
Resveratrol
Indole-3 Carbinol (I3C)
Peucedanum Chenur
Astaxanthin
Quercetin
Ellagic Acid
Caryophyllene Sesquiterpenes
Phlorotannins
The Antioxidant/Pro-oxidant Enigma of Cancer Therapy
Phytochemicals as Immunotherapy Adjuvants
Conclusion and Future Perspectives
References
6 Therapeutic Application of Microbial Metabolites in Free Radical-Induced Tumorigenesis
Introduction
Role of ROS in Tumorigenesis
Antioxidant Compounds from Microbial Sources
Role of Secondary Metabolites of Actinobacteria in Anticancer Activity
Role of Exopolysaccharides of Lactic Acid Bacteria in Anticancer Activity
Effect of Bacterial Toxins and Enzymes on Anti-tumorigenesis
Role of Biosurfactants from Microorganisms in Antitumor Therapy
Conclusion and Future Perspectives
References
7 Therapeutic Potential of Natural Agents Against Oxidative Stress-Influenced Colitis-Associated Cancer
Introduction
Colitis-Associated Cancer (CAC)
Sources of Free Radicals in the Colon
Food
Obesity
Age
Reactive Oxygen Species (ROS)
Role of ROS in CAC
Natural Agents and Its Mechanism of Action on CAC
Mechanism of Action of Procyanidin B on CAC
Mechanism of Action of Shaoyao Decoction on CAC
Mechanism of Action of Red Ginseng Oil on CAC
Mechanism of Action of Caffeic Acid Phenethyl Ester on CAC
Mechanism of Action of Lyophilized Acai Pulp on CAC
Protocatechuic Acid on CAC
Betaine on CAC
Sasa quelpaertensis Leaf Extract on CAC
Oligonol on CAC
Embelin on CAC
Phytosomal Curcumin on CAC
Rutaecarpine on CAC
Vanillin on CAC
Huangqin Decoction on CAC
American Ginseng on CAC
Hydroxychloroquine on CAC
Conclusion
Future Directions
References
8 Oxidative Stress: A Double Edged Sword in Cancer
Introduction
Tetrandrine as ROS Scavenger
Tetrandrine-Induced ROS-Mediated Autophagy
Tetrandrine-Induced ROS-Mediated Apoptosis
Conclusion
References
9 Prevention of Fertility due to Chemotherapy-Induced Ovarian Failure: Role of Therapeutic Antioxidants
Introduction
Types of Cytotoxic Drugs
Pathways of Chemotherapy-Induced Ovarian Damage
Chemotherapy-Induced Oxidative Stress
Cellular Background of Oxidative Stress
Redox State and Oxidative Stress
Antioxidant System and Use of Antioxidants During Chemotherapy
Adjuvant Antioxidants
Vitamin C and Vitamin E
Melatonin
Other Antioxidants
Conclusion and Future Perspective
References
10 Therapeutic Implications of Phytochemicals in ROS-Induced Cancer
Introduction
Reactive Oxygen Species in Cancer
Carcinogenesis and Phytochemicals
Chemoprevention: Types and Approaches
Dietary Phytochemicals: Role in Cancer Chemoprevention
Phytochemicals: Polyphenols
Flavonoids
Apigenin
Isoflavonoids
Anthocyanidins
Phytoestrogens
Resveratrol
Curcumin
Terpenoids
Carotenoids
Lycopene
Limonoids
Glucosinolates
α-Linolenic Acid (ALA)
Allicin
Silymarin
Sulforaphane (SFN)
Conclusions
References
11 Nutraceuticals in Cancer Therapy
Introduction
Nutraceuticals and Cancer
Flavonoids and Polyphenols
Catechins
Theaflavins and Thearubigins
Flavonoids
Non-flavonoidal Anti-cancer Nutraceuticals
Organosulfur Compounds
Sulforaphane (SLFN)
Glucobrassicin and Indole-3-Carbinol
Diallyl-Disulfide and Thiosulfinates
Carotenoids
Resveratrol
Curcumin
Cancer and Diet
Molecular Biology Effects
Effect of Nutritional Support on Cancer Patients
Nutraceuticals: Challenges and Perspectives
Conclusion
References
12 Potential Natural Product-Derived Compounds for Lung Cancer Therapy
Lung Cancer
Types and Staging of Lung Cancer
Lung Cancer and Oxidative Stress Potential Sources
Oxidative Stress and Biological Effects
Apoptotic Cell Death and Oxidative Stress
Apoptosis
Potentials Targets of Drug Action in Relevance to Reactive Oxygen Species and Redox Regulation
Misfolded Proteins, Reactive Oxygen Species (ROS), and the Endoplasmic Reticulum Stress (ER Stress)
ER Stress as a Target for Lung Cancer Treatment
CSC and Oxidative Stress in Lung Cancer
Natural Product Derived Compounds
New Anticancer Compounds from Plants
Gallic Acid
Curcumin
Flavonoids
Green Tea Polyphenols
Genistein
Tangeretin
Resveratrol
Lectins
Natural Product-Derived Compound Regulating Mitochondrial Pathway
Gracillin
Quercetin
Resveratrol
Pterostilbene
Honokiol
Betulinic Acid
Marine-Derived Compounds for Cancer Treatment
Ecteinascidin Alkaloids
Psammaplin A
Didemnin B
Dolastatin 10
Halichondrin B
References
13 Role of Dietary Antioxidants in Chemoprevention of Nitrosamines-Induced Carcinogenesis
Introduction
Causes of Chemical Carcinogenesis
Carcinogenicity of N-nitroso Compounds
Dietary Cancer Prevention
Chemoprevention
Dietary Intervention
Lycopene
Vitamins
Carotenoids
Isothiocyanates
Polyphenols
Flavonoids
Calcium
Astaxanthin
Conclusion
Future Direction
References
14 Natural Antioxidants for the Prevention and Treatment of Cancer
Introduction
Free Radicals, Oxidative Processes, and Cell Changes
Secondary Metabolites, Sources, and Nutritional Implications
Herbal Bioactive Compounds and their Molecular Targets
Benefits and Risks of Concomitant Use of Secondary Metabolites and Cytotoxic Drugs
Novel Uses of Secondary Metabolites in Cancer Research
Conclusions and Future Directions
References
15 Protective Effect of Quercetin, Luteolin, and Fisetin via Stimulating the p53-Mediated Signaling in Cancer
Introduction
Structure of p53
Regulation of p53 Level and Activity
Physiological Functions of p53
Cell Cycle Regulation
Induction of Apoptosis
p53 in Response to DNA Damage
p53 Targets Survival Signaling
p53 and Its Cross Talk with Other Signaling Pathways
p53 and Its Cross Talk with NF-κB
p53 and Oxidative Stress
Conclusion
Future Perspective
References
16 Flavonoids and Its Anticancer Activity for ROS-Induced Breast Cancer
Introduction
ROS Level and Cellular Homeostasis
ROS in Cancer Signaling Pathway
Flavonoids as Anticancer Agents
Chemistry and Classification
Absorption, Metabolism, and Bioavailability of Flavonoids
Anticancer Effects of Flavonoid
Effect of Flavonoids on Breast Cancer
Molecular Mechanism of Action
Flavonoids for Breast Cancer
Conclusion
References
17 Role of Indian Ginseng Withaferin A in ROS-Induced Cancer Chemoprevention and Cancer Therapy
Introduction
Plant Distribution and Phylogeny
Chemical Constituents of Ashwagandha Roots
Pharmacological Effects of Withania somnifera
Anti-inflammatory Properties
Antioxidant Activity
Adaptogenic Property
Antiangiogenic Property
Immunomodulatory Activity
Other Activities of Withania somnifera
Reactive Oxygen Species (ROS): Double-Edged Sword
Reactive Oxygen Species (ROS)
Antioxidant System
Signaling Pathways Mediated by ROS
PI3/Akt Pathway Mediated by ROS
MAPK Pathway Mediated by ROS
Keap1-Nrf2-ARE Pathway Mediated by ROS
NF-B Pathway Mediated by ROS
ROS, a Driving Force for Tumorigenesis
ROS-Mediated Chemoprevention
Withaferin A in ROS-Induced Chemoprevention
Conclusion
References
18 Role of Carotenoids in Preventing Oxidative Stress–Induced Cancer
Introduction
Oxidative Stress
Antioxidants
Carotenoids
Sources of Carotenoids
Carotenoid Biosynthesis
Structural Features of Carotenoids
General Functions of Carotenoids
β-Carotene
Lycopene
Lutein
Zeaxanthin
β-Cryptoxanthin
Astaxanthin
Canthaxanthin
Fucoxanthin
Future Perspectives of Carotenoids
References
19 Role of Honey in Prevention and Management of Cancer
Introduction
Bioactive Components of Honey
Sugars
Polyphenols
Amino Acids
Proteins and Enzymes
Vitamins and Minerals
Mechanistic Perspective of Honey in Combating Cancer
Honey Induces Apoptotic Cell Death
Honey Regulates the Mitochondrial Pathways and Related Proteins
Honey Induces ROS, and This Arrests Cell Cycle
Anti-inflammatory and Immune-Modulatory Effects of Honey
Role of Honey in Combating Metastasis and Stem Cell Populations
Honey as a Combinatorial Approach for the Management of Cancer
Cautions for the Use of Honey
Conclusions
References
20 Natural Extracts Target NF-κB and Reactive Oxygen Species
Introduction
Reactive Oxygen Species (ROS) and Their Role in Cancer
Promotion of Tumor Cell Proliferation by ROS
ROS-Mediated Regulation of Apoptosis and Cell Survival
Role of ROS in Cell Motility and Metastasis
Role of ROS in Angiogenesis
ROS in Cancer Stem Cells (CSCs) and Promotion of Chemoresistance
ROS-Mediated Antitumorigenic Activity
NF-kappa B (NF-κB) Signaling and Tumor Progression
NF-κB Signaling
NF-κB and Oncogenesis
Chemoresistance Mediated by NF-κB and ROS
Folate Antagonists or Antifolates
Pyrimidine Antagonists
Alkylating Agents
Intercalating Agent
Mitotic Spindle Inhibitors
Use of Natural Extracts to Prevent Chemoresistance and Drug-Induced Toxicity
Natural Extracts Suppress Chemoresistance Due to ROS
Curcumin
Resveratrol
Wogonin
Epigallocatechin-3-gallate (EGCG)
Genistein
Natural Extracts Suppress Chemoresistance Due to NF-κB
Anacardic Acid
Butein
Cardamonin
Curcumin
Resveratrol
Therapy-Induced Toxicity by ROS and Its Prevention by Natural Extracts
Doxorubicin-Induced Cardiotoxicity
Bleomycin-Induced Pulmonary Fibrosis
Cisplatin-Induced Acute Kidney Injury (AKI)
Paclitaxel-Induced Painful Neuropathy
Cisplatin-Induced Ototoxicity
Therapy-Induced Toxicity by NF-κB and Its Prevention by Natural Extracts
Bleomycin-Induced Pulmonary Fibrosis
Cisplatin-Induced Acute Kidney Injury (AKI)
5-Fluorouracil-Induced Intestinal Mucositis
Irinotecan-Induced Intestinal Mucosal Injury
Cisplatin-Induced Ototoxicity
Conclusion and Future Direction
References
21 Natural Compounds from Plumbago zeylanica as Complementary and Alternative Medicine
Introduction
Morphology and Botanical Description
Phytochemistry
Traditional Use of P. zeylanica
Therapeutic Properties of P. zeylanica
Anticancer Activity
Antioxidant Activity
Antibacterial Activity
Antifungal Activity
Antidiabetic Activity
Antifertility Activity
Antiviral Activity
Wound Healing Activity
Other Therapeutic Properties
Nanobiotechnological Potential
Copper Nanoparticles
Silver Nanoparticles
Gold Nanoparticles
Conclusion
References
22 Immunomodulatory Algal Metabolites for Alleviating Inflammation and Cancer
Introduction
Pro-Tumorigenic Inflammation
Macroalgae Anti-Inflammatory Properties
Red Macroalgae Anti-Inflammatory Activity
Brown Macroalgae Anti-Inflammatory Activity
Green Macroalgae Anti-Inflammatory Activity
Macroalgae Anticancer Properties
Red Macroalgae Anticancer Activity
Brown Macroalgae Anticancer Activity
Green Macroalgae Anticancer Activity
Microalgae Anti-Inflammatory Activity
Microalgae Anticancer Activity
References
23 Targeting Natural Compounds to Mitochondria as a Novel Strategy for Cancer Therapy
Introduction
Mitochondrial Functions
Role of Mitochondria in Tumorigenesis
Targets Inside the Mitochondria
Mitochondrial Metabolism
Mitochondrial Electron Transport Chain
Tricarboxylic Acid Cycle
Glycolysis
Mitochondrial ROS Homeostasis and Redox-Signaling Pathways
Mitochondrial Dependent Intrinsic Apoptotic Signaling Pathway
Induction of Apoptosis Through TP53
Epidermal Growth Factor Receptor (EGFR)
Mitochondrial DNA (mtDNA)
Mitochondrial Dynamics
Barriers in Directing Drugs to the Mitochondria for Cancer Treatment
Natural Compounds for Cancer Therapy
Strategies for Mitochondria-Specific Anti-Cancer Drug Delivery
Mitochondrial Targeting of Anticancer Drugs Using Delocalized Lipophilic Cations (DLCs)
Targeting of Anticancer Drug Using Mitochondria-Penetrating Peptides
Mitochondrial Targeting of Anticancer Drug Using Mitochondria Targeted Nano-Carriers
DQAsome (DeQAlinium-Based lipoSOMES)
Liposomes
Polymeric Nanoparticles
Inorganic Nano-Carriers
Graphene Oxide
Gold Nano-Carriers
Mesoporous Silica Nanoparticles (MSNs)
Dendrimers
MITO-Porter
Conclusion and Future Perspectives
References
24 Recent Updates on the Bioactive Compounds of Ginger (Zingiber officinale) on Cancer: A Study with Special Emphasis of Ginge...
Introduction
Carcinogenesis
Mechanism of Cancer
Cancer: Reactive Oxygen Species (ROS)
Cancer Biomarkers
Medicinal Plants for the Treatment of Cancer
Ginger
Compounds of Ginger
Anticancer Effects of Ginger
Ginger-Bioactive Compound: Gingerol and Its Anticancer Effects
Therapeutical Potential of Gingerol and Its Effect on Metabolic Pathways in Cancer
Free Radical Scavenging and Antioxidant Activity of Gingerol
Effect of Gingerol on Apoptotic Genes
Effect of Gingerol on Tumor-Suppressor Genes
Effect of Gingerol on Cycloxygenase Enzyme
NF-B and Gingerol in Cancer Prevention
Impact of Gingerol on Angiogenesis
Conclusion and Future Perspectives
References
25 Cytotoxic, Antitumor, and Chemopreventive Effects of Pointed Gourd (Trichosanthes dioica) Root
Introduction
Plant Profile: Pointed Gourd
Systematics
Common Names
Habitat
Commercial Importance
Medicinal Uses
Relevant Activities
In Vitro Cytotoxic Effect
Antimitotic Effect
Antitumor Effect
Cancer Chemopreventive Effect
In Vitro Antioxidant Effect
Discussion
Conclusion
References
26 Therapeutic Implications of Piperlongumine
Introduction
Sources of PL and Taxonomic Classification of P. longum L.
Isolation and Chemical Structure Determination of PL
Total Chemical Synthesis of PL
Structure Activity Relationship (SAR) Studies on PL
Anticancer Activities of PL
Colon Cancer
Lung Cancer
Breast Cancer
Pancreatic Cancer
Renal Carcinoma
Prostate Cancer
Gastric Cancer
Melanoma (Skin Cancer)
Leukemia (Blood Cancer)
PL in Combination with Other Anticancer Drugs
Metabolic and Safety Profile of PL
Other Therapeutic Properties
Biosynthesis of PL
Future Directions
Conclusion
References
27 Antioxidant/Pro-oxidant, Anti-inflammatory, and Immunomodulatory Effects of Thymoquinone in Cancer Prevention and Treatment
Introduction
Cancer Preventing Effect of TQ
Antioxidant Effects of TQ in Cancer Prevention
Anti-inflammatory and Immunomodulatory Effects of TQ in Cancer Prevention
Anti-inflammatory Effects of TQ in Cancer Prevention
Immunomodulatory Effects of TQ in Cancer Prevention
Cancer Treatment Effect of TQ
Pro-oxidant Activity of TQ in the Treatment of Cancer
Conclusion
References
28 Therapeutic Implications of Spirulina in ROS-Induced Cancer Progression
Introduction
What Is Spirulina?
Spirulina Species, Morphology, and Taxonomy
Production of Spirulina
Spirulina Contents
Where Spirulina Is Used?
Beneficial Effects of Spirulina on Health
Antitoxic, Heavy Metal Chelating Properties
Hypolipidemic Hypoglycemic Effects
Antimicrobial Effects
Antiviral
Antibacterial
Probiotic
Nutritional Supplement
Antihypertensive
In Cancer Treatment
Sonodynamic and Photodynamic Therapy (PDT) in Cancer
Radioprotector Effects
Effects of Antioxidant and Anti-reactive Oxygen Species (ROS)
ROS
ROS and Cancer
ROS and Cancer Progression
ROS and Cytotoxic Effects
Antioxidant Effects of Spirulina on Cancer
Side Effects
Conclusion
References
29 The Role of Cannabis Species on Oxidative Stress in Cancer Cells
Introduction
Cannabis and Cannabinoids
Cannabinoid Receptor System
Application of Cannabis Species in Medicine
The Endocannabinoid System
Anticancer Properties and Mechanism of Cell Death
Acute Versus Chronic Oxidative Stress in Cancer
Genes Involved in Cancer Oxidative Stress
Oxidative Stress in the Tumor Microenvironment
Cannabis Derivatives and Oxidative Stress
Conclusion
References
30 Natural Chemopreventive Agents for the Treatment and Prevention of Oral Squamous Cell Carcinoma
Introduction
Ficus Species
Curcumin
Genistein
Resveratrol
Quercetin
Ellagic Acid
Lycopene
Green Tea
Bromelain
Garlic and Onions
Dracaena cinnabari
Conclusion
References
31 Phytochemicals as Pro-oxidants in Cancer
Introduction
Pro-oxidant Nature of Phytochemicals: Molecular Mechanisms
Classification of Pro-oxidants
Phytochemicals as Pro-oxidants
Polyphenolic Compounds
Flavonoids
Carotenoids
Ascorbic Acid
Alpha-Tocopherol (Vitamin E)
Conclusion
References
32 Protective Role of Pomegranate in ROS-Induced Prostate Cancer
Introduction
Modulation of Inflammation and Proliferation by PJ
PJ-Induced Activation of SIRT3-SOD Pathway
PJ in Modulating Cell Cycle Progression
PJ-Induced Modulation of NFκB
Gene Expression and PJ
Modulation of Cell Adhesion, Migration, and Invasion by PJ
MicroRNAs, Prostate Cancer, and PJ
Role of PJ in PLA2-MMP Signalling Pathway Induced Prostate Cancer
In Silico Investigation of the Possible Molecular Interactions of Ellagic Acid and Urolithin A with CDK1, COX2, and NF-κB
Conclusion and Future Perspectives
References
33 The Effect of Oxidative Nutritional Products on Cancer
Introduction
Intracellular Signal Pathway of ROS in Cancer
Target of ROS Modulating Cancer
Natural Compounds Inhibiting GSH Pathway
Natural Products Focused on the Thioredoxin Pathway
Natural Products Disturbing SOD Activity
Natural Products Blocking Catalase
Natural Products Disturbing the NRF Pathway
Vitamin Exhibiting Antioxidant and Pro-oxidant Effects
Conclusions
References
34 Natural Products as an Alternative Therapy for Brain Tumors
Introduction
Clinical Presentation
Diagnosis
Classification
Epidemiology
Risk Factors
Treatment
Surgical Management
Upfront Management by Tumor Type
Pilocytic Astrocytoma (WHO I)
Diffuse Low-Grade Gliomas (WHO II)
Diffuse High-Grade Gliomas (WHO III)
Glioblastoma (WHO IV)
Natural Products as Anticancer Agents
Alkaloids as Anticancer Agents
Flavonoids as Anticancer Agents
Saponins as Anticancer Agents
Rosmarinic Acid
Cannabis and Cannabinoids
Neurostatins in Brain Tumor
Latex and Resins in Brain Tumors
Guduchi
Bittersweet in Brain Tumors
Andrographolide and Brain Tumors
Plumbagin in Brain Tumors
Natural Products and Blood-Brain Barrier
Natural Products on Cancer Stem Cells
Current Status of Natural Products on On-Going Clinical Trials in TBI
Conclusion
References
35 Current Evidence and Future Perspectives About Herbal Therapeutics for Cancer Therapy
Introduction
Phytochemicals for the Treatment of ROS-Induced Cancer
Tea Polyphenols
Resveratrol
Quercetin
Curcumin
Nanocarrier Based Targeted Delivery Approaches for Phytoconstituents
Liposomes
Dendrimers
Carbon Nanotubes
Polymeric Micelle
Recent Developments in Analytical/Screening Techniques for the Explorative Analysis of Natural Chemopreventive Agents
Extraction Techniques
Liquid Chromatography-Mass Spectrometry (LC-MS)
Tandem Mass Spectrometry (LC-MS/MS)
Liquid Chromatography-Nuclear Magnetic Resonance Spectrometry (LC-NMR) Analysis
Gas Chromatography-Mass Spectrometry Analysis (GC-MS)
High-Resolution Mass Spectrometry (HRMS)
Summary and Discussion
Future Perspective
References
36 Herbal Remedies for Improving Cancer Treatment Through Modulation of Redox Balance
Introduction
Redox Status in Normal Healthy Cells
Redox Modulation in Cancer Cells
Cancer Treatment
Herbal Remedies as Adjuvants in Cancer Treatment Therapy
Curcumin (Curcuma longa)
Tulsi (Ocimum sanctum)
Licorice (Glycyrrhiza glabra)
Picrorhiza (Picrorhiza kurroa)
Giloy (Tinospora cordifolia)
Sweet Violet (Viola odorata)
Ferulic Acid (FA)
Conclusion
References
37 Targeting Redox Homeostasis of Tumor Cells by Therapeutic Compounds in Cancer
Introduction
ROS and Cancer Cell Signaling Pathways
PI3K/Akt Pathway
MAPK/ERK Signaling Pathway
NF-kB Pathway
Medicinal Plants of Indian Origin
Withania Somnifera (Ashwagandha)
Aegle Marmelos
Centella Asiatica
Zingiber Officinale
Conclusion
References
38 Natural Compound-Based Nanoparticles to Target Free Radicals in Cancer
Introduction
Cancer Cells are Subjected to Oxidative Stress
Oxidative Stress Modulates Cellular Signaling
Altered Redox Is a Selective Target in Cancer
Redox Chemotherapeutics
Natural Product as Redox Chemotherapeutics
Natural Compound-Based Nanoparticles as Redox Therapeutics
Conclusion
Future Prospectus
References
Part II: Therapeutic Implications of Synthetic Compounds
39 Small Molecule Inhibitors That Target Signal Transduction Pathways Involved in Oxidative Stress-Induced Cancer
Introduction
ROS and Oxidative Stress-Induced Cancer
Role of ROS in Cancer Progression
Role of ROS in Inducing Cancer Cell Proliferation
Role of ROS in the Induction of Redox-Mediated Cellular Mechanisms
Role of ROS in the Induction of Genetic Instability
Role of ROS in the Induction of Tumor Hypoxia
Role of ROS in the Induction of Cancer Metastasis
Role of ROS in the Tumor Microenvironment
Role of ROS in Cell Survival and Apoptosis
Small Molecule Inhibitors Targeting ROS and ROS-Mediated Signaling
Small Molecule Inhibitors Targeting Tyrosine and Serine/Threonine Kinases
Small Molecule Inhibitors Targeting Proteasomes
Small Molecule Inhibitors Targeting Apoptosis
Concluding Remarks: Limitations and Future Perspectives of Small Molecule Inhibitors
References
40 Pristimerin in Oxidative Stress and Use in Cancer
Introduction
Chemical Aspects of Pristimerin
Cellular and Molecular Mechanisms
Oxidative Stress Induction
Related Cell Signaling Pathways
NF-κB Signaling
PI3K/Akt/mTOR Signaling
MAPK Signaling
Wnt/β-Catenin Signaling
miRNA
Metastasis, Migration, Invasion, and Angiogenesis
Breast Cancer
Prostate Cancer
Lung Cancer
Colon Cancer
Melanoma
Head and Neck Cancer
Other Mechanisms
Conclusion
References
41 Polyphenolic Acetates as Potential Therapeutics and Adjuvant in Radiotherapy of Cancer
Introduction
Cytotoxic Effects of Polyphenolic Acetates
Cell, Tissue, and Systemic Responses to Radiotherapy of Cancer
Polyphenolic Acetates as Modifiers of Radiation Response
Radio-Sensitization of Tumor Cells by Polyphenolic Acetates (PA)
Mitigation of Acute Radiation Syndrome by DAMTC: Hematopoietic and GI Recovery Following Radiation Damage
Conclusion
References
42 Applications of Peptide in Cancer Therapy
Introduction
Why Peptides?
Classification of Therapeutic Peptides
AMP/Pore-Forming Peptides
Cell Penetrating Peptides (CPPs)
Cationic CPPs
Amphipathic CPPs
Hydrophobic CPPs
Biomedical Applications of CPPs
Tumor-Targeting Peptides (TTPs)
Different Possible Options to Use Therapeutic Peptides in Cancer Treatment
Peptides as Vaccine in Cancer Therapy
Peptide as Radionuclide Carrier in Cancer Therapy
Peptide as Cytotoxic Drug Carrier in Cancer Therapy
Peptide as Hormone in Cancer Therapy
Peptide as Drug in Cancer Therapy
Conclusion and Future Direction
References
43 The Influence of Protein Disulfide Isomerase Inhibitors on Oxidative Stress in Breast Cancer Metastasis
Introduction
Reactive Species in Breast Cancer Metastasis
Protein Disulfide Isomerase in Breast Cancer Metastasis
PDI Inhibitors as Drug Candidates for Treatment in Breast Cancer Metastasis
Conclusion and Future Perspectives
References
44 Beyond Natural Antioxidants in Cancer Therapy: Novel Synthetic Approaches in Harnessing Oxidative Stress
Introduction
Therapy and Oxidative Stress
Enzyme-Related Antioxidants
Glutathione (GSH) and N-Acetylcysteine (NAC)
NOX Enzymes´ Inhibition
NOX4 shRNA/siRNA
Antioxidant Peptides
Hybrid Antioxidant Compounds
Antioxidant Polymers
Nanoparticles Containing Inherent Antioxidant Activities
Cerium Oxide (CeO2)
Fullerene (C60)
Platinum Nanoparticles (PtNPs)
Mesoporous Silica Nanoparticles (MSNPs)
Photodynamic Therapy (PDT)
Chemotherapy-Associated Oxidative Stress
Conclusion
References
45 Arylboronic Acids and Ester-Based Prodrugs Targeting Oxidative Stress in Cancer
Introduction
Background
Molecular Mechanism of ROS-Mediated Drug Release
Prodrugs: A Challenge and Achievements
Masking and De-Masking of Drugs
Prodrug-Based Chemo War Against Cancer
Selective Scaffolds as Arylboronic Acid (and Ester) Prodrugs
Quinone Methides
Nitrogen Mustard
Aliphatic Nitrogen Mustard
Aromatic Nitrogen Mustard
Aminoferrocene-Based Arylboronic Ester Prodrug
Nucleoside-Based Arylboronic Acid (Ester) Prodrugs
Stilbene-Based Arylboronic Acid (Ester) Prodrug
Alkaloid-Based Arylboronic Acid (Ester) Prodrugs
Taxol-Based Arylboronic Acid (Ester) Prodrugs
Miscellaneous Drug as Boronic Acid (Ester) Prodrug
Arylboronic Acid-Ester-Based Theranostic Prodrugs
Arylboronic Acid-Ester-Based Drug Delivery System
Conclusion and Future Direction
References
46 An Overview of Antioxidative Anticancer Therapies with Reference to the Cancer Stem Cells
Introduction
Oxidative Stress and Onset of Carcinogenesis
Oxidative Stress and Cancer Stem Cells
Oxidative Stress and Cancer Epithelial-to-Mesenchymal Transition
Oxidative Stress and Tumor Cell Invasion
ROS and Cancer Angiogenesis
Oxidative Stress and Cancer Cell Proliferation
Hypoxia and Oxidative Stress
ROS-Modulated MicroRNA in Cancer
Oncogene, Tumor Suppressor Gene, and Oxidative Stress
Oxidative Stress and Epigenetic Modification in Cancer
Tumor Microenvironment and Oxidative Stress
ROS as Cancer Therapeutics
Antioxidants as Preventives and Cancer Therapeutics
Pro-oxidants in Cancer Therapeutics
Conclusion
References
47 Application of Stimuli-Responsive Polymers in Cancer Therapy
Introduction
Light-Responsive Polymers
Temperature-Sensitive Polymers
Ultrasound-Sensitive Polymers
pH-Responsive Therapy
Redox Responsiveness
Enzyme-Responsive Polymers
Magnetic Field-Responsive PMs/NPs
Conclusion and Future Perspectives
References
48 Evaluation of the Anticancer Activities of Isatin-Based Derivatives
Introduction
Isatin (1H-indole-2,3-dione/2,3-dioxindole), a Biomolecule with Biological Activity
Structure of Isatin and Its Role as a Scaffold for Synthesis of Novel Anticancer Agents
Isatin-Based Derivatives and Their Structure-Function Diversities
Synthesis of IBDs
IBDs as Kinase Inhibitors
Isatin-Based Derivatives: Types and Anticancer Efficacies
Isatin-Based Imines
N-Substituted Isatins
Isatin Dimers/Bis-Isatin Derivatives
Isatin Hydrazones
Isatin-Based Spiro Compounds and Spirooxindole Derivatives
Isatin-Linked Chalcones/Isatin-Chalconoids
Isatin-Thiosemicarbazones
Isatin Conjugates/Hybrids
Isatin-Based Metal Complex Ligands
Multisubstituted Isatin Derivatives
Redox Control of Drug (and IBDs) Action and Metabolism
Redox Reactions and Pharmacological Agents
Murburn Concept and Multiple Reactions of IBDs with ROS/Redox Enzymes
Conclusion
References
49 Efficacy of Synthetic Organic Molecule Inhibitors of TRAF2 and NCK-Interacting Kinase (TNIK) Against Colorectal Cancer
Introduction
Colorectal Cancer Incidence
Mechanism of CRC Induction
Wnt Signalling Pathway and TNIK
TNIK in Wnt Signalling: A Key Pharmacological Target in CRC
Cellular Kinases: Gatekeepers of Critical Cellular Processes
Wnt Signalling and Oxidative Stress: A Coherent Relationship
Nature of TNIK Expression in CRC
Structural Basis of TNIK Catalysis and Inhibition with Reference to the Prime Kinases
Assessment of TNIK Inhibitors
Patterns and Quantum Chemical Basis of TNIK Inhibitors
Future Directions and Challenges
Conclusions
References
50 Recent Advances in the Development of Synthetic Pro-oxidants: Implications for ROS-Based Cancer Therapeutics
Introduction
ROS Generation and Regulation
Role of ROS in Cancer
Prooxidant Approach for Cancer Therapy
Conclusion and Future Perspectives
References
51 Synthetic Small Molecules in Prostate Cancer Therapeutics
Introduction
Prostate Cancer Progression
Current Treatments
Small Molecules and Its Relevance in Targeted Therapy
ETS Oncogene Targets
AR Splice Variant Targets
Small Molecules
BRD32048
ERGi-USU
VPC-18005
YK-4-279
KI-ARv-03
Conclusion
References
52 Therapeutic Efficacy of Roscovitine Against Cancer
Introduction
Main Text
Oxidative Stress and Cancer
Oxidative Stress and Cell Cycle
CDKs in Oxidative Stress-Induced Cancer
Role of CDKs in Cell Cycle Progression
CDKs in Cancer
CDK Inhibitors as Potential Chemotherapeutics
Drug Resistance by Tumors
Plant-Based Novel Chemotherapeutic Agents
Discovery, Structure, Chemistry, and Characteristic of ROSC
Mechanism of Action of ROSC
In vitro Anticancer Activity of ROSC
In vivo Antitumor Activity of ROSC
Pharmacokinetic Study and Clinical Trials of ROSC
Conclusion
References
53 Oxidative Stress Modulation by G-quadruplex Binder-Naphthalene Diimide Derivatives and Its Therapeutic Potential
Introduction
G-quadruplex Structures Present in the Telomeric Ends and Untranslated Regions of Proto-oncogenes have Regulatory Roles
Oxidative Stress and Cancer
Oxidative Stress Induces Perturbations in G-quadruplex Structures
NDI Derivatives as G-quadruplex Ligands
Conclusion
References
54 A Critical Appraisal of Current Status of Synthetic Antioxidant Molecules in the Treatment of Breast Cancer
Introduction
Breast Cancer
Epidemiology of BC
Types of BC
Luminal A Type
Luminal B Type
Triple-Negative Basal-Like
HER2 Type
Various Risk Factors Associated with Development of BC
Role of Oxidative Stress in the Development and Progression of BC
What Is Oxidative Stress?
How Does ROS Formation Takes Place?
Role of ROS in the Development and Progression of BC
Various Signaling Mechanisms Activated/Inhibited by ROS During Development and Progression of BC (Fig. 2)
Currently Available Treatment Strategies for BC by Targeting Different Signaling Mechanisms
Checkpoint Inhibiting Agents
Micro RNA Targeting
Targeting BRCA-1 Gene
Targeting P53 Protein
CXCR4 Receptor Inhibiting Agents
Targeting GPER Receptors
Targeting P13K/Akt/mTOR Pathways
Poly-ADP Ribose Polymerase (PARP) Inhibiting Agents
Mitogen-Activated Protein Kinase (MAPK) Inhibiting Agents
Pathway for Notch Signaling
Signaling Pathway of Hedgehog/gli 1
Chimeric Antigen Receptor T-Cell (CART) Therapy
Synthetic Antioxidant Molecules Under Clinical Trials for Treatment of BC
Synthetic Heterocyclic Molecules for Treatment of BC Targeting Oxidative Stress
Phenothiazines
Flavonoids
Xanthones
Quinazolinones
Benzofurans
Dihydroquinazolinones
Uracil
Ebselen
Pyrazolotriazine
Pyrrolidinedione
Chalcone
Morpholine
Pyrazolines
Arylselenium
Selenomethionine and Selenocysteine
Organophosphonates
Isoxazole
Conclusion
References
Part III: Radiation and Photodynamic Approaches in ROS-Induced Cancer Therapeutics
55 Modulatory Effects of Stem Cells on Oxidative Stress and Antioxidant Defense System in Cancer
Introduction
Role of Oxidative Stress in Carcinogenesis
Implication of Oxidative Stress in Different Stages of Carcinogenesis
Effect of Different Types of Stem Cells on Oxidative Stress and ROS Production
Stem Cells
Stem Cell Therapy
Stem Cells and Cancer
Modulatory Effects of Stem Cells on Oxidative Stress and Antioxidant Defense System During Carcinogenesis and Cancer Progressi...
Conclusion and Recommendations
References
56 Emerging Interdisciplinary Techniques to Extend ROS Modulation for the Benefit of Chemo-/Radiotherapy in Cancer
Introduction
Exogenous Generation of ROS
Endogenous Generation of ROS
Types of ROS
Free Oxygen Radicals
Nonfree Radical ROS
Tumor-Associated Inflammation
Cellular Responses in the Form of DNA Repair
Radiotherapy
Direct Effects
Indirect Effects
Radiosensitivity and Resistance
Role of Mesoporous Silica in Nanomedicine
Mesoporous Silica Nanoparticle (MSN) Utility in Photodynamic Therapy (PDT) and Sonodynamic Therapy (SDT)
Redox Adaptation in Cells and Its Modulation for Cancer Treatment
Role of Miscellaneous Novel Small Molecular Compounds in ROS Modulation
Oxamate
D-Allose
Histone Deacetylase Inhibitors
Role of Natural Herbs in Modulating ROS in Cancer Treatment
Flavonoids
Polyphenols
Naphthoquinones
Terpenoids
Ginsenosides
Radiosensitization Through the Regulation of Cell Stress Responses
Antioxidant System Inhibition in Cancer Cells
Role of Superoxide Dismutase (SOD), an Antioxidant Enzyme, in Cancer
Conclusion and Future Perspectives
References
57 Photodynamic Therapy-Induced Oxidative Stress for Cancer Treatment
Introduction
Photosensitizers
Principle of PDT and Generation of Oxidative Stress
Type I Reactions
Type II Reactions
Singlet Oxygen (1O2)
Reactions of Singlet Oxygen with Biomolecules
Molecular Targets of PDT-Induced Oxidative Stress
Effect of Oxidative Stress on Gene Expression
PDT-Induced Cell Death Mechanisms and Signal Transduction After PDT
Apoptosis
Necrosis
Autophagy
Clinical PDT
Measures to Increase Efficiency of PDT
Conclusions and Future Prospects
References
58 Elevating the Reactive Oxygen Species in Cancer Cells by Photodynamic Therapy
Introduction to Photodynamic Therapy (PDT)
Mechanism of Phototherapy Action
Photosensitizing Agents Used in PDT
First Generation of Photosensitizers
Second Generation of Photosensitizers
Third-Generation of Photosensitizers
Limitations of Photosensitizers
Phytochemicals
Molecular Mechanism
Role of Nanotechnology in PDT
PDT in Different Types of Cancer
PDT in Skin Cancer
PDT in Esophageal Cancer
PDT in Prostate Cancer
Mechanism of PDT Cell Death Pathway in Different Cancers
Apoptosis
Autophagy
Necrosis
Future Perspectives
References
59 Plasmonic Photothermal Therapy (PPTT) of Cancer
Introduction
Era of Nanotechnology
Metallic Nanoparticles
Metallic Nanoparticle Advantages
Characteristics of Metallic Nanoparticles
Ideal Properties of Nanoparticles
Gold Nanoparticles (Au NPs)
Silver Nanoparticles (ag NPs)
Synthesis of au/ag NPs
Nanotechnology in Medicine
Nanotechnology in Cancer Diagnosis
Plasmonics
Plasmonic Photothermal Process
Nanotechnology Tools Used in Cancer Diagnosis
Using Gold Nanorods
Using Gold Nanoshells
Near-Infrared (NIR) Quantum Dots
Nanotechnology in Cancer Therapy
Nanotechnology as a Tool for Cancer Therapy
Using Carbon Nanotubes
Graphene and Graphene Oxide
Polymeric Nanoparticles
Conclusions
References
60 Role of ROS in Combined Radiation Effect in Cancer Therapy
Introduction
Role of ROS to Modulate Cell Death
ROS in Autophagy
ROS in Apoptosis
ROS in Ferroptosis
ROS in Necroptosis
ROS in Pyroptosis
Role of ROS in Different Cancer Therapies
ROS in Radiotherapy
ROS in Chemotherapy
ROS in Immunotherapy
Effect of ROS in Combined Radiation Therapy
Summary and Conclusion
References
61 Application of Photodynamic Therapy for Treatment of Oral Cancer
Introduction
Photodynamic Therapy
Brief History
Basic Mechanism of PDT
Components of PDT
Photosensitizer
Oxygen
Light Sources
Mechanisms of PDT-Induced Tumor Destruction
Direct Cell Death
PDT-Induced Damage to Tumor Vasculature
PDT-Induced Inflammation and Antitumor Immunity
Clinical Studies and Advantages of PDT of Oral Cancer
PDT Is Noninvasive, Selective with Less Side Effects
PDT as Primary, Adjuvant/Combined Modality
PDT as a Palliative Treatment Modality
Challenges Associated with PDT of Oral Cancer
Recent Developments in PDT and Future Prospects
Targeted PS
Photoimmunotherapy
Nanotechnology-Based Delivery
Conclusion
References
62 Advances in Photodynamic Protocols for Nonmelanoma Skin Cancer
Nonmelanoma Skin Cancer
Topical PDT in Nonmelanoma Skin Cancer
Protocols Optimization for Nonmelanoma Skin Cancer
Improvements of the Drug Delivery
Nonmelanoma Skin Cancer and the Evolution of Topical PDT in Brazil
Conclusion
References
63 Metallic Core-Shell Nanoparticles as Drug Delivery Vehicles in Targeted Photodynamic Therapy of Cancer
Introduction
Targeted Photodynamic Therapy
Basics of PDT
Challenges of PDT
Targeted PDT
Active Targeting
Passive Targeting
Metallic Core-Shell Nanoparticles
Preparation of Metallic CSNPs
Formulations of Metallic CSNPs with Photosensitizers
Characterization of CSNPs and CSNPs-PS Drug Delivery Systems
Metallic CSNPs-PS in TPDT
PDT Efficiency of CSNPs-PS Conjugates
Subcellular Localization of CSNPs-PS Conjugates
Colloidal Stability of CSNPs-PS Drug Delivery Systems in TPDT
Conclusions and Future Directives
References
64 Recent Advancements in Nanomaterials for Photodynamic Therapy of Cancers
Introduction
Principle of Photodynamic Therapy
Conventional Photosensitizers and their Limitations
First-Generation Photosensitizers
Second-Generation Photosensitizers
Third-Generation Photosensitizers
Current Limitations of Photodynamic Therapy
Nanoparticles in Photodynamic Therapy
Nanoparticles as a Delivery Agent
Biodegradable Nanoparticles
Non-biodegradable Nanoparticles
Active Nanoparticles
Nanoparticles As Down-Converting Photosensitizers Agent
Nanoparticles As up-Converting Photosensitizers
Conclusion and Future Perspectives
References
65 Photodynamic Therapy in Cancer
Introduction
Mechanism of Photodynamic Action
Tumor Destruction Mechanism
Direct Killing of the Tumor Cells
Cell Killing Mechanisms in PDT
Vascular Damage
Immune and Inflammatory Response
Photosensitizers
First-Generation Photosensitizers
Second-Generation Photosensitizers
Third-Generation Photosensitizers
Limitations of PDT
Formulation of Photosensitizer
Nanoparticles in PDT
Biodegradable Nanoparticles
Nonbiodegradable Nanoparticles
Conclusion
References
66 Radiotherapy-Induced Augmentation of Cellular Oxidative Stress
Introduction
Radiotherapy
Types of Radiotherapy
External Beam Radiation Therapy (EBRT)
Conventional External Beam Radiation Therapy
Intensity-Modulated Radiation Therapy (IMRT)
Image-Guided Radiation Therapy (IGRT)
Stereotactic Radiosurgery (SRS)
Stereotactic Body Radiation Therapy (SBRT)
Proton Therapy
Internal Radiation Therapy
How Radiation Therapy Works?
Direct Effects of Radiation
Types of Cell Death in Cancer
Indirect Effects of Radiation
Radiolysis of Water and Generation of ROS
Radiation-Induced Production of Reactive Nitrogen Species (RNS)
Role of Radiation in Chronic Inflammation
Cellular Defenses to Handle DNA Alterations
Radioprotection of Normal Cells
Antioxidant Status and Radiotherapy
Conclusion
References
67 Photodynamic Therapy and ROS
Introduction
Role of PDT in Early Stages of Lung Cancer
Signalling Pathways
PDT Pathway
Immune System
Molecular Level
MAPK and AKT Pathway:
NF-KB Pathway
Sources of ROS
Detoxification from ROS
ROS Effects on Tumors
Conclusion and Future Perspective
References
Part IV: Epigenetic Tools and Gene Therapy in ROS Management: Implications in Cancer Progression
68 Oxidative Stress-Mediated miRNA Regulation in Cancer
Introduction to miRNA World
miRNA as a Gene Regulator
miRNA-Mediated Gene Regulation Mechanism
Oxidative Stress and Cancer
Oxidative Stress or ROS Effect miRNA in Cancer
ROS in Chromosomal Aberration
ROS in Epigenetic Modification
ROS in Controlling miRNA Biogenesis
ROS in Regulating miRNA Functions Via Transcription Factors
c-Myc
P53
NF-κB
HIF-1α
Conclusion and Future Perspectives
References
69 Reactive Oxygen Species: Induced Epigenetic Modification in the Expression Pattern of Oncogenic Proteins
Introduction
ROS in Cancer Development
ROS Generation and Epigenetic Changes
ROS and Proto-Oncogenes
ROS Generation and Epigenetic Changes in TP53
ROS Generation and Epigenetic Changes in RAS
ROS Generation and Epigenetic Changes in c-Myc
ROS Generation and Epigenetic Changes in NF-κB
ROS Generation and Epigenetic Changes in EMT Oncogenes
Conclusion
References
70 Targeting ROS-Induced Epigenetic Reprograming in Cancer Stem Cells
Introduction
Generation of ROS in Cancer
Endogenous Sources of ROS in Cancer
Mitochondria
NADPH Oxidase
Other Oxidative Organelles and Enzymes
Peroxisomes
Cyclooxygenases
Lipoxygenases
Thymidine Phosphorylase
Other Oxygen Radicals
Epigenetic Reprograming of CSCs and Oxidative Stress
A Crosstalk Between ROS Mediated Signaling and Epigenetic Switch in CSCs as Part of Reprograming
Epigenetic and Metabolic Reprograming in CSCs
Conclusions and Future Directions
References
71 Therapeutic Implications of Long Non-coding RNA in the Regulation of Lung Cancer
Introduction
lncRNAs
lncRNA-Regulated Signaling Network During Lung Carcinogenesis
Cell Proliferation and Apoptosis
Epithelial-Mesenchymal Transition (EMT), Cell Migration and Invasion
lncRNAs in Redox Regulation of Lung Cancer
Therapy Resistance
lncRNAs in Lung Cancer Management
Biomarker in Lung Cancer Detection
Downregulation of Tumor-Promoting lncRNAs by Genetic Engineering Tools
Suppression of Lung Cancer-Promoting Signal by lncRNAs
lncRNAs as Therapy as Well as Therapeutic Targets
Major Challenges
Conclusions and Future Prospects
References
72 Role of Histone Methylation in Cancer: Pathobiology and Therapeutics
Introduction
Histone Methylation and Cancer
SET Domain-Containing KMTs
EZH2
MLL2
SMYD2 and SETD2
G9a and SUV39H1
SETD8
Non-set Domain-Containing KMTs
KDM2A
KDM3A
KDM4A
KDM5A
KDM6A
Histone Methyltransferase as New Therapeutic Target for Cancer
Conclusion and Future Perspective
References
73 microRNAs-Mediated Regulation of Voltage Gated Anion Channel 1: A Major Player in ROS Generation and Cancer Progression
Introduction
Role of microRNAs in Different Pathologies
microRNA-Mediated Regulation of VDAC1 and Its Impact on Cancer Progression
miR-320a and VDAC1
miR-7 and VDAC1
miR-490-3p and VDAC1
miR-197-3p and VDAC1
Prospect of microRNA Therapeutics in Cancer, Especially Targeting VDAC1
References
74 Epigenetic Regulators of NRF2
Introduction
NRF2 Signaling Pathway
Epigenetic Regulation of NRF2/KEAP1 in Cancer
DNA Methylation
Histone Modifications
Histone Methylation
Histone Acetylation
Noncoding RNAs (ncRNAs)
Potential Epi-Regulators of NRF2 in Cancer
HDAC Inhibitors (HDACi)
DNMT Inhibitors
BET Bromodomain Inhibitors (BETi)
Discussion and Conclusion
References
75 Exosomal Non-coding RNAs
Introduction
Breast Cancer
Oxidative Stress Induced Breast Cancer
Exosomes
Non-coding RNA in General
miRNA
lncRNA
siRNA
piRNA
YRNA
Exosomal Non-coding RNA and Their Sorting Mechanism
General Mechanism Involved in Exosomal Sorting of ncRNAs
Mechanism Involved in Oxidative Stress Induced Breast Cancer
General Mechanism
Mechanism Involving Exosomal ncRNAs
miRNAs
LncRNAs
Role of Individual Exosomal Non-coding RNA in Regulating Oxidative Stress Induced Breast Cancer
miRNA
siRNA
Exosomes Theranostics
Milestones (Fig. 7)
Challenges and Future Perspective/Scope
Conclusion
References
76 miRNA-Mediated Oxidative Stress Management in Cancer
Introduction to miRNA-mediated Gene Regulation
An Overview
miRNA as a Regulator of Oncogenes
Oxidative Stress Contribution in Cancer
Oxidative Stress and Cancer
Oxidative Stress Controlling in Cancer
miRNA and Oxidative Stress
miRNA Controlling Oxidative Stress
miRNA Transport Regulation, Oxidative Stress, and Cancer
Conclusion and Future Perspectives
References
77 A Critical Approach in the Analysis of lncRNA Characteristics for Cancer Therapy
Introduction
Overview of ROS-Induced Cancers and Their Associations with lncRNAs
Overview of lncRNAs
Functionality of lncRNAs
Biochemical Importance of lncRNAs
Involvements of lncRNAs in ROS-Induced Cancers
lncRNAs in Prostate Cancer
PCAT-1
PCA3
PCGEM1
lncRNAs Involved in Breast Cancer
HOTAIR
ANRIL
MALAT1
Colorectal Cancer
CCAT1
Liver Cancer
HULC
HEIH
Bladder Cancer
UCA1
lncRNAs as Biomarkers and in Gene Therapy
lncRNAs and Cancer Metastasis
Conclusion
References
78 Long Noncoding RNA Acting as Therapeutic Target for Oxidative Stress-Induced Pancreatic Cancer
Introduction
Treatment Strategy of Pancreatic Cancer
Overview of Long Noncoding RNA (lncRNA) in Cancer
Biological and Functional Roles of lncRNAs in Pancreatic Cancer
Reactive Oxygen Species and Long Noncoding RNA in Cancer
Long Noncoding RNA in Cancer Therapy Mediated via Oxidative Stress
Long Noncoding RNA as Diagnostic and Prognostic Biomarkers for Pancreatic Cancer
Long Noncoding RNAs in the Directive of Oxidative Stress, Reactive Oxygen Species and Pancreatic Cancer Progression
Mechanistic Role of Hypoxia-Induced Long Noncoding RNA in Pancreatic Cancer
Conclusion and Future Perspective
References
79 Short Non-coding RNAs: Emerging Molecular Players in Therapeutics of ROS-Induced Cancer
Introduction
Short Non-coding RNAs and Cancer
MicroRNAs in ROS-Induced Cancer
Regulation of miRNA Expression Through ROS-Induced Transcription Factors
c-Myc
p53
NF-κβ
HIF-1α
β-Catenin and FOX
Regulation of miRNA Expression Associated with ROS Through Epigenetic Modifications
DNA Methyltransferases (DNMTs)
Histone Deacetylases (HDACs)
Modulation of miRNA Biogenesis by ROS
Modulation of ROS Level by miRNAs
NOX/miR-34a
POX/miR-43b
miR-128a
miR-141/miR-200a
Modulation of Mitochondrial Functions by ROS-Induced miRNAs
Modulation of Antioxidants by ROS-Induced miRNAs
Challenges of Using miRNAs in Therapy in ROS-Induced Cancer
Small Interfering RNAs (siRNAs) in ROS-Induced Cancers
siRNAs Targeting NRF2
siRNAs Targeting NOX
siRNAs Targeting Romo1
siRNAs Targeting CSNK2β
Piwi-Interacting RNAs (piRNAs) in ROS-Induced Cancer
Small Nucleolar RNAs (snoRNAs) and Small Nuclear RNAs (snRNAs) in ROS-Induced Cancer
Conclusion
References
80 Implications of NRF2 in Cancer Progression and Therapeutics
Introduction
NRF2 Activation in Cancer
Regulation of NRF2 Proteins
KEAP1 Dependent NRF2 Dissociation
KEAP1-Independent Regulation of NRF2 Protein Stability
NRF2 Implication in Cancer
NRF2 Inhibitors
Brusatol
Wogonin
Luteolin
Chrysin
Apigenin
Oridonin
Procyanidin
Trigonelline
Convallatoxin
Honokiol
Halofuginone
Parthenolide
Camptothecin
Conclusion
References
81 Non-coding RNAs as Trojan Horse in Eliminating ROS-Induced Cancer
Introduction
Role of ROS in Cancer
Angiogenesis
Cell Proliferation
Epigenetic Modification
Metastasis
Non-coding RNA (ncRNA)
Non-coding RNAs in ROS Inhibition
MicroRNAs (miRNAs)
Small Interfering RNAs (siRNAs)
Long Noncoding RNAs (lncRNAs)
Circular RNAs (circRNAs)
PIWI-Interacting RNA (piRNAs)
Conclusion and Future Perspective
References
82 Role of ROS-Mediated Epigenetic Alterations in the Development of Solid Tumor
Introduction
Role of DNA Methylation in Tumorigenesis
Effect of Reactive Oxygen Species (ROS) on DNA Methylation in Tumor Cells
Effect of Reactive Oxygen Species (ROS) in Tumorigenesis
Effect of ROS in Regulation of Expression of MicroRNAs in Tumorigenesis
Role of Epigenetic Alterations of Mitochondrial DNA in Tumorigenesis
Conclusions and Perspectives
References
83 Role of Notch Signalling in Oxidative Stress and Stem Cell Self-Renewal During Colitis and Colon Cancer
Introduction
Reactive Oxygen Species
ROS, Colitis, and Colon Cancer
Development of Colon Tumors
Cancer Stem Cells
CSCs and Colon Cancer
Feedback Loop between Inflammation and Cancer Stem Cells
Oxidative Stress Targets Cell Signalling
Notch Signalling in Normal Intestine
Notch Signalling in Colorectal Cancer
Notch and Chemoresistance
Wnt-Notch Crosstalk
Conclusions and Future Scope
Bibliography
84 Oncogenic Virus-Induced Oxidative Stress and Epigenetic Regulation: An Insight into Host DNA Methylation
Introduction
ROS/RNS Production
Heat Stress
Genotoxic Stress
Hypoxic Stress
Metabolic Stress
Pathogenic Stress
Oxidative Stress and Epigenetic Reprogramming by Oncogenic Virus
Oncogenic Virus and Associated Cancers
Hepatitis C Virus
Hepatitis B Virus
Human Papillomavirus
Epstein-Barr Virus (EBV)/Human Herpesvirus 4 (HHV-4)
Kaposi´s Sarcoma-Associated Herpes Virus/Human Herpesvirus 8 (HHV-8)
Human T-Cell Leukemia Virus Type 1
Techniques to Identify the ROS Levels Inside the Cells
Fluorescence 2D Gel Electrophoresis
AP Site Assay
Flow Cytometric Analysis of Cellular ROS Levels
Determination of GSSG/GS
Iodoacetate Tandem Mass Tag (iodoTMT)
RAC-1 Activity Assay
H2O2 Measurement
Conclusion
References
85 Radiation-Induced Epigenetic Changes and Their Modulation by Epidrugs
Introduction
Radiation-Induced Changes in DNA Methylation
Role of DNA Methylation in Radiation-Induced Carcinogenesis
Radiation-Induced Modifications in Histones
Phosphorylation
ADP-Ribosylation
Acetylation
Methylation
Ubiquitination
Small RNA-Mediated Alterations
Modulation of Radiation-Induced Damages by Epidrugs
Conclusion and Future Prospectives
References
86 Mucinous Colorectal Cancer Oxidative Stress and Therapeutic MicroRNAs
Introduction
Types of Colorectal Cancer
Colorectal Adenocarcinoma
Non-mucinous Adenocarcinoma
Mucinous Adenocarcinoma and Its Subtypes
Major Influencers of Colorectal Cancer
Loss of Heterozygosity (LOH)
Microsatellite Instability (MSI)
CpG Island Methylator Phenotype (CIMP)
KRAS
BRAF
P53 and P21
Mucin Genes in Colorectal Cancer (CRC)
Secreted Gel-Forming Mucins
Transmembrane Mucins
MicroRNAs in Mucinous Carcinoma
Early Prognosis of Mucinous Carcinoma
Diagnostic and Therapeutic Potential of Mucins
Existing Clinical Treatments
Conclusion and Future Perspectives
References
87 Insights into the Oxidative Stress and microRNA-Based Therapeutics in Colorectal Cancer
Introduction
MicroRNA
Oxidative Stress
Reactive Oxygen Species(ROS)
MicroRNA Biogenesis and ROS
MicroRNA Regulation by ROS Through Transcriptional Factors
ROS and Epigenetic Alterations
Interplay or Cross Talk Between ROS and MicroRNA Associated with Cancer
Cell Proliferation and Survival
Programmed Cell Death
Tumor Invasion and Metastasis
Expression Profile of MicroRNA and ROS Levels Observed in Colorectal Cancer
ROS and MicroRNA Interaction in Colon Cancer
MicroRNA as a Biomarker
MicroRNA in Tissues
MicroRNAs in Serum or Plasma
MicroRNA in Stool
Pros and Cons of the MicroRNA Biomarkers
ROS and MicroRNA-Mediated Therapeutic Strategies
Future Perspectives and Conclusion
References
88 Oxidative Stress Associated Non-coding RNAs in Pathogenesis of Urologic Cancers: Prognostic and Therapeutic Importance
Introduction
Oxidative Stress and Age-Related Disease
Urologic Cancer, Disease Conditions Related to Oxidative Stress
Non-coding RNA, a Potential Link Between Oxidative Stress and Prostate Cancer
miR-21; Gene Locus, Biogenesis, and Oxidative Stress
miR-21 in Prostate Carcinogenesis; a Potential Link with Oxidative Stress
miR-21 vs. Cellular Antioxidant Defense
miR-21 in Oxidative Stress Linked Signalling Pathways
miR-21 in AR and PI3K/Akt Signalling Pathways
AR Pathway
PI3K/Akt Pathway
Crosstalk of AR and PI3K/Akt Pathways
Modulation of AR and PI3K/Akt Pathways by miR-21
miR-21 in RTK/ERK Signalling Pathway
RTK/ERK Pathway
RTK/ERK Pathway Modulation by miR-21
miR-21 in TGF-β Signalling Pathway
TGF-β Pathway
Modulation of TGF-β Signalling by miR-21
miR-21 in Cell Death Pathway
Oxidative Stress and Cell Death Pathway
miR-21 Suppresses Apoptosis
Prognostic Importance of miR-21 in Prostate Cancer
Therapeutic Importance of miR-21 in Prostate Cancer
miR-21 in Predicting Efficacy of Conventional Therapy
miR-21 as a Target of Novel Therapeutics
Therapeutics Using Synthetic Compounds
Therapeutics Using Natural Compounds
Conclusion and Future Perspectives
References
89 Implications of Oxidative Stress and Epigenetic Drivers in Ovarian Cancer Progression and Therapy
Introduction
Driver Mutations in Ovarian Cancer Progression and Treatment
Oxidative Stress and Tumor Progression
Role of Oxidative Stress in Ovarian Cancer Progression
Epigenetics and Tumor Progression
Role of Epigenetic Alterations in Ovarian Tumorigenesis
Interrelationship between Oxidative Stress and Epigenetic Alterations in Ovarian Cancer Progression and Treatment
Therapeutic Utilization of Epigenetic and Redox Modifiers in Ovarian Cancer
Conclusion and Future Direction
References
90 Noncoding RNA regulation and Oxidative Stress
Introduction
Noncoding RNAs (ncRNAs)
Characterization of lncRNAs
Characterization of Small ncRNA
Oxidative Stress
Sources of ROS in Cancer Cells
Cellular Detoxification Systems
ROS and ncRNA Expression
Effect of ncRNAs on ROS Generators and Antioxidants
ROS and Cancer Development
Tumor Initiation
Proliferation of Tumor Cells
Hypoxia and Tumor Progression
Resistance to Apoptosis
Metabolic Reprogramming or Cellular Energetics
Invasion, Metastasis, and Angiogenesis
Acquisition of Cellular Stemness
Conclusion
References
91 MicroRNAs: The Master Regulators of the Breast Cancer Tumor Microenvironment
Introduction
Breast Cancer Overview
Breast Cancer Subtypes
Current Breast Cancer Screening
miRNA Biogenesis
miRNAs in Breast Cancer
The TME
Hypoxia and Oxidative Stress
miRNAs Regulating Hallmarks of Cancer
Oxidative Stress Regulating the TME
Oxidative Stress and miRNAs
Tumor-Associated Angiogenesis and Lymphangiogenesis
Oxidative Stress and Tumor-Associated Angiogenesis
Roles of miRNAs in Angiogenesis and Lymphangiogenesis in Breast Cancer
CSCs and Oxidative Stress
CSCs and miRNAs
miRNA Therapeutic Relevance in Cancer
Biomarker Capability of miRNAs in Breast Cancer
Conclusion and Future Perspectives
References
92 Role of MicroRNA in ROS Modulation and Its Implication in Lung Cancer and Therapeutics
Introduction
Sources and Regulation of ROS
Intracellular Sources of ROS in Cancer
ROS-Promoting Signaling Pathways
ROS Regulation by Cellular Antioxidant Machinery
Dual Role of ROS in Cancer
Pro-tumoregenic Role of ROS
Tumor-Suppressor Role of ROS
MicroRNAs: Structure, Function, and Biogenesis
Role of MicroRNAs (miRNAs) in Tumorigenesis
Crosstalk Between miRNA and ROS in Lung Cancer
Association Between miRNAs, ROS, and Deregulation of Metabolic Pathways
Association Between MicroRNAs, ROS, and Hypoxia
Association Between MicroRNAs, ROS, and Oncogenic Signal Transduction Pathways
Association Between MicroRNA, ROS, and Antioxidant Pathways
Association Between MicroRNAs, ROS, and Epithelial-to-Mesenchymal Transition
Association Between MicroRNAs, ROS, and Cell Death Pathways
Apoptosis
Autophagy
Ferroptosis
Lung Cancer Therapeutics in Modulating ROS and MicroRNA
Conclusion and Future Perspectives
References
Part V: Stem Cells in Therapeutics of ROS-Induced Cancer
93 Interplay of MicroRNAs and Reactive Oxygen Species in Cancer Stem Cells: New Perspective in Cancer Metastasis
Introduction
Cancer Stemness
Cancer Metastasis
MicroRNAs
Reactive Oxygen Species
miRNA Regulating ROS in Cancer Stem Cells Linked with Metastasis
ROS Regulating miRNA in Cancer Stem Cells Associated with Metastasis
Interplay Between ROS and miRNA in Regulating Cancer Stemness and Metastasis
Conclusion and Future Direction
References
94 Therapeutic Potential of Chemical Compounds in Targeting Cancer Stem Cells
Introduction
Impact of ROS on CSCs
Endogenous Molecules Regulates ROS
Signaling Pathways
Wnt/β-Catenin
Hh
Notch
TGF- β
PTEN/PI3K/Akt/mTOR
MAPK/ERK/STAT
Transcription Factors and Genes
FOXO
FOXM1
Nrf2
p73
p53
NF-κB
c-MYC
HIF
Antioxidant and Prooxidant Proteins
AMPK
SOD
Peroxidases
NADPH Oxidases (NOX)
Protein Kinase C (PKC)
ALDH
Isocitrate Dehydrogenase (IDH)
GSH
Programmed Death-Ligand 1 (PD-L1)
Bcl-2
Coenzyme Q10 (CoQ10)
NAC
Anticancer Drugs and Agents
Rapamycin
Amifostine
Doxorubicin
Paclitaxel (Taxol)
Cisplatin
Bevacizumab
IPI-504 (Retaspimycin Hydrochloride)
As2O3
Ps-341
Other Compounds and Molecules
Hydroxyurea (HU) and Hydroxamic Acids (HAs)
NSAIDs
Arsenic (as)
Selenium (se) and se Derived Compounds
Taurolidine and Piperlongumine
Kinase Inhibitors
Photochemical Internalization (PCI)
Thiol- Molecules
Chloroquine
Nitrones
Conclusion
References
95 Functional Correlation Between ROS and Cancer Stem Cells in Cancer Progression
Introduction
Stem Cells vs Cancer Stem Cells
ROS-Induced Tumorigenesis
ROS-Mediated Angiogenesis
ROS-Mediated Metastasis
ROS-Mediated Inflammation
Hypoxia and ROS in the Maintenance of Cancer Stem Cell Pool
Markers of Cancer Stem Cells and ROS
Epithelial-Mesenchymal Transition (EMT)
High ROS Also Contributes to EMT in CSCs
Therapeutic Targeting of CSCs
Conclusion and Future Perspectives
References
96 Colon Cancer Stem Cells
Introduction
Role of Oxidative Stress in Colorectal Cancer
Role of Oxidative Stress in the Formation of Colon Cancer Stem Cells
Characterization of Stem Cells in the Colon
Role of Stem Cells in Colon Cancer
Targeting Colon CSCs in Management of Colorectal Cancer
Wnt/β-Catenin Signaling
Hedgehog Signaling
Notch Signaling
Transforming Growth Factor-β Signaling
Crosstalk Among Pathways
Conclusion and Future Perspectives
References
97 Therapeutic Modalities Regarding ROS in Leukemia and Hematopoietic Stem/Progenitor Cell Perspective
Introduction
Reactive Oxygen Species (ROS): A Brief Account
ROS and Mechanisms of ``Redox Homeostasis´´
Hematopoiesis: A General Overview
ROS and Hematopoiesis: A Walk Through
ROS and Hematological Malignancies
Therapeutic Modalities Concerning ROS
ROS-Modulating Therapeutic Management in Hematological Malignancy
References
98 Stemness and Stromal Niche: Targets in Oxidative Stress-Induced Oral Cancer
Introduction
Imbalance in Generation and Elimination of Reactive Oxygen Species (ROS) Leading to Oxidative Stress in Oral Cancer
Cancer Stem Cells in Oral Carcinoma and Interplay of Oxidative Stress
Mechanism of Redox Balance in Maintenance of Cancer Stemness
Oral Cancer Microenvironment and its Role in Maintenance of Stemness
Therapeutic Options in Oxidative Stress-induced Cancer
Targeting Redox Homeostasis Against Stemness
Conclusion and Future Perspectives
References
99 Targeting Signaling Pathways in Cancer Stem Cells for Therapy of Cancer
Introduction
Signaling Pathways in Cancer Stem Cells
Developmental Signaling Pathway
TGFβ Pathway
Hippo Pathway
AMPK Pathway
Autophagy
Properties of CSCs Regulated by Signaling Pathways
Stem Cell Maintenance
Tumor Microenvironment
Immune Evasion
Resistance to Therapy
Clinical Targeting of Signaling Pathways in CSC
Conclusion
References
100 Cancer Stem Cell Oxidative Phosphorylation: Target for Cancer Therapy
Introduction
Cancer Stem Cells
Metabolism
Glycolysis and Cancer
Oxidative Phosphorylation and Cancer
Electron Transport Chain
Other Roles of Mitochondria
Inhibition of Oxidative Phosphorylation
Inhibition of Mitochondrial Function
Inhibition of Mitochondrial Transfer
Inhibiting Respiratory Chain Complexes
Inhibition Based on Membrane Potential
Indirect Inhibition of OXPHOS
Combination with Tyrosine Kinase Inhibitors and Metabolic Activities
Summary and Conclusion
References
101 Targeting Oxidative Stress Specific NRF2 in Pancreatic Cancer Stem Cells
Introduction
Overview of the Nrf2 Protein
Cross Talk Between Nrf2-Keap1
Role of Nrf2 and Oxidative Stress
Role of Nrf2 and Tumor Progression
Role of Nrf2 and Molecular Signaling in Cancer
Cancer Stem Cells
Role of Nrf2 in CSCs
Role of Nrf2 and Chemoresistance in CSCs
Nrf2 Is a Prospective Target for CSCs Treatment
Conclusion and Future Aspects
References
102 Redressal of the Molecular Mechanisms of Colon and Other Cancer Stem Cell Energetics/Oxidative Stress for Possible Transla...
Introduction
Molecular Mechanisms of Cellular Energetics of Somatic Cells, Regenerative and Cancer Stem Cells
Correlation of Cellular Energetics with the Aggressiveness of Cancer Stem Cells
The Metabolic State of Cancer Stem Cells: Flexibility Versus Scarcity!
Cellular Energetics of Colon Cancer Stem Cells
Targeting Metabolic Regulators for CSC Eradication
Targeting Metabolic Pathways with Conventional Drugs
Targeting Redox Homeostasis
Targeting Drug Transporters
Targeting Signaling Pathways
Targeting Epigenetic Modulations
Conclusions and Perspectives
References
103 Regenerative Medicines for ROS-Induced Cancers Treatment
Introduction
Inducing ROS Levels for Oxidative Stress-Induced Cell Death
Suppressing Elevated Levels of ROS
Stem Cells
Totipotent Stem Cells
Pluripotent Stem Cells
Multipotent Stem Cells
Unipotent Stem Cells
Stem Cells Transplantation
Stem Cell Use for Cancer Treatment
Stem Cells Programmed for Enzyme/Prodrug Therapy
Stem Cells for Viral Therapy
Stem Cells as Nanoparticle (NP) Carrier for Cancer Treatment
Stem Cell-Derived Exosomes Use in Cancer Therapy
Stem Cells as Targeted Therapy
Challenges and Risk Factors to Stem Cells Therapy
Conclusion
References
104 Oxidative Stress-Related Mechanisms That Mediate Chemoresistance in Cancer Stem Cells
Introduction
Oxidative Stress-Related Mechanisms and Chemoresistance in Hematological Neoplasias
Acute Lymphocytic Leukemia (ALL)
Acute Myeloid Leukemia
Chronic Myeloid Leukemia (CML)
Multiple Myeloma
Lymphomas
Cancer Stem Cell-Driven Oxidative Stress Mechanisms of Chemoresistance in Solid Tumors: Lessons from Brain and Breast Cancer
Brain Tumors
Breast Tumors
Conclusions
References
105 Cancer Stem Cells in Therapy Resistance of Colorectal Cancer
Introduction
Dysregulated Signaling Pathways of CSCs
The Wnt/β-Catenin Signaling Pathway
The Hippo/YAP Signaling Pathway
The Hedgehog Signaling Pathway
Other Signaling Pathways
miRNA
DNA Damage Repair of CSCs
Maintaining Low Level of ROS
Maintenance of Relative Quiescent or Dormant State
Therapeutic Targeting of CSCs and Limitation of Targeting CSCs
Conclusion and Future Perspective
References
106 Role of Stem Cells and Reactive Oxygen Species in Cancer
Introduction
Stem Cell Therapy
Stem Cells in Cancer Therapy
ROS in Cancer
ROS and Nuclear Factor Erythroid 2-Related Factor 2 (Nrf-2) Signaling
Nrf-2 Signaling in MSCs
Nrf-2 Signaling in Cancer Stem Cells
Conclusion
References
107 Therapeutic Strategies Targeting Wnt/β-Catenin Signaling Pathway in Stem Cells for ROS-Induced Cancer Progression
Introduction
Overview of Reactive Oxygen Species
Sources of ROS
Endogenous Sources of ROS
Exogenous Source of ROS
Wnt Signaling Pathway Regulating ROS Production
ROS and DNA Damage
Contribution of ROS in Stem Cell Modulation
Wnt Signaling in Cancer and Stem Cells
Role of Wnt Signaling Pathway and ROS Generation in Cancer
ROS in Tumor Progression
Apoptosis
Tumor Metastasis
Wnt Activators and Inhibitors
Wnt Inhibitors
Wnt Activators
Role of Wnt Signaling in Governing Stem Cell Fate
ROS and Stem Cell Fate
ROS Regulation and Therapeutic Implication of Wnt Activators/Inhibitors
Conclusion
Future Perspectives
References
108 Delineating the Role of PI3K Signaling Pathway in the Stem Cell Therapeutics of ROS-Induced Carcinomas
Introduction
Stem Cells: A Promising Drug Delivery Vehicle in Carcinoma Therapy
Types of Stem Cells Used in Carcinoma Therapy
Stem Cell Modifications in Cancer Treatments
ROS-Mediated Mechanism in Cellular Processes
ROS Function in Cancer Progression
Source of Reactive Oxygen Species in Cancer Cells
Mitochondrial ROS
Role of Warburg Effect in ROS
NADPH Oxidase and Xanthine Oxidase Produce ROS
ER Stress and ROS
ROS and Genetic Instability
ROS and Cancer
Crosstalk of PI3K Signaling Pathway in the Regulation of ROS Generation
Therapeutic Strategies in the Regulation of ROS Mediated Cancer
References
109 Therapeutic Strategies for ROS-Dependent Tumor Angiogenesis Using Vascular Stem Cells
Introduction
ROS-Dependent Tumor Angiogenesis
Signaling Mechanisms Modulating ROS-Mediated Angiogenesis in Cancer Progression
Vascular Stem Cells
Types of VSCs
Interplay of ROS and VSC in Tumor Angiogenesis
Therapeutic Strategies
Inhibition of Endogenous Production of ROS
Targeting Antioxidant Enzymes
MSCs: A Double-Edged Sword in Tumor Angiogenesis
Perspectives and Future Direction
References
110 Mesenchymal Stem Cell-Mediated Suicide Gene Therapy
Introduction
Suicide Gene Therapy (SGT)/ Gene Directed Enzyme Prodrug Therapy (GDEPT)
Methods Involved in MSC Mediated SGT
Transduction of Mesenchymal Stem Cells with Gene of Interest (GOI)
Viral Methods of Transgene Delivery into MSCs
Lentiviral-Based Vectors
Adenoviral Vectors
Adeno-Associated Virus
Oncogene Retrovirus Based Vectors
Non-viral Methods of Transgene Delivery into Mesenchymal Stem Cells
Tissue-Specific Targeting of Genetically Engineered MSC
Tumor Growth
Cardiovascular Diseases
Blood
Neurological Disorders
Enzyme/Prodrug Systems
Herpes Simplex Virus Thymidine Kinase (HSV-TK)/Ganciclovir(GCV)
Cytosine Deaminases (CD)/5-Fluorocytosine (5-FC)
Cytochrome P450 (CYP450)/Oxazaphosphorine
Clinical Studies Using MSC-Based Therapies for Cancer Treatment
Future Prospects
Conclusion
References
111 Biopolymer-Based Nanocarriers for Stem Cells or Stem Cell Differentiating Agents and Their Therapeutic Significance
Introduction
Embryonic Stem Cells
Very Small Embryonic-Like Stem Cells
Nuclear Transfer Stem Cells
Reprogramming Stem Cells
Adult Stem Cells
Tissue Engineering and Regenerative Medicine
Tissue Engineering and Stem Cell Differentiation
Regenerative Medicine and Stem Cell Differentiation
Nanotechnology and Tissue Engineering
Nanotechnology and Regenerative Medicine
Biopolymers for Medical Applications
Biopolymers for Delivery of Stem Cells
Biopolymers as Carriers for Stem Cell Differentiating Agents
Microtechnology
3D Printing
Way Forward
References
112 Reactive Oxygen Species and Cancer Stem Cells: Molecular Interactions and Their Implications in Cancer
Introduction
Reactive Oxygen Species and Cancer
Anomalous Redox Regulation of CSCs in Cancers
Role of ROS in the Transformation of Normal or Tumor Cells to CSCs
ROS and CSCs in the Tumor Microenvironment
ROS Act as a Vital Signal Transducer in Crucial Cell Signaling Pathways
Wnt/β-Catenin Signaling Pathway
Notch Signaling Pathway
ATM Signaling Pathway
PTEN/PI3K/AKT/mTOR Signaling Pathway
JAK/STAT Signaling Pathway
NFκB Signaling Pathway
Contribution of ROS and CSCs to Tumor Aggressiveness
Combating CSCs by Targeting ROS in Various Tumors
Therapeutic Potential of Targeting the Redox Metabolism in Cancer
Conclusions
References
113 The Complex Interplay Between JAK-STAT Pathway and ROS in Regulating Stem Cells During Inflammation and Cancer
Introduction
Models of Cancer Dissemination
Redox Regulation in CSCs
ROS-Mediated Hypoxia Inducible Factor Stabilization in Tumor Niche Drives CSCs
Inflammation Associated Mechanisms and Signalling Molecules Regulated by Immune Cells Mediate Cancer Progression and Drive CSCs
The Crosstalk Between ROS, JAK-STAT Signalling, and Inflammation in CSCs
Conclusion and Future Scope
References
114 Emerging Metabolic Regulation of Redox Status in Cancer Stem Cells Progression and Metastasis
Introduction
Metabolic Plasticity and Stemness Features in CSCs
Glycolytic Pathway in CSCs
Role of Oxidative Phosphorylation in Regulation of CSCs
Glutamine Metabolism in CSCs
Lipid Metabolism in CSCs
Metabolic Control by ROS and Modulation of CSCs Fate
ROS-Dependent Metabolic Regulators Drive CSCs
Role of HIF1α in Regulation of Redox Metabolism
Role of MYC in Regulation of Redox Metabolism
Role of TP53 on Regulation of Redox Metabolism
Other Redox Metabolic Regulators
Epithelial-to-Mesenchymal Transition and CSCs
Conclusion and Future Prospective
References
115 Exosomes Regulate ROS in Cancer Stem Cells
Introduction
Biogenesis of Exosomes
Components of Exosomes
Biology of Exosomes
Cancer Stem Cells
ROS and CSC
Exosomes of CSC
Exosomes and ROS
Oxidative Stress and Cancer
Exosome, CSC, and ROS
Conclusion and Future Perspectives
References
116 Photodynamic Oxidative Stress Targets Cancer as Well as Cancer Stem Cells
Introduction
Cancer and Cancer Stem Cells
Cancer
Cancer Stem Cells
Reactive Oxygen Species
Redox Metabolism of Cancer Cells
Redox Metabolism of CSCs
Redox Profile of the Tumor Mass
Photodynamic Therapy
Photodynamic Therapy and Cancer
PDT and Its Photosensitizers
PDT and ROS
Photodynamic Oxidative Stress and CSCs
Conclusion
References
117 Adipose-Derived Stem Cells as Photodynamic Therapeutic Carriers for Treatment of Glioblastoma Exploiting Reactive Oxygen S...
Introduction
Glioblastoma
Involvement of ROS in Cancer Progression
Involvement of ROS in Glioblastoma Treatment
Adult Stem Cells and ADSCs
Using Stem Cells in Cancer Treatment
Using ADSCs as Delivery Vehicles for Anticancer Drugs
ADSCs Used as a Post-Cancer Treatment Regenerative Tool
Photodynamic Therapy
Photodynamic Therapy and Reactive Oxygen Species
Photodynamic Therapy Treatment for Glioblastoma
ADSCs as a PS Drug Carrier for Treating Glioblastoma
Discussion
Conclusion
References
118 Targeting the Metabolism in Cancer Cells for Cancer Therapy
Introduction
Cellular Sources of ROS Generation and Their Metabolic Detoxification
ROS as a Volatile Inducer of Cancer
Metabolic Pathways, ROS, and Redox Homeostasis
Glycolysis and Oxidative Phosphorylation
Pentose Phosphate Pathway
Glutamine Metabolism
Targeting the Reprogrammed Cancer Cell Metabolism and Its Redox Reactions for Cancer Therapy
Targeting the Cancer Cell Metabolism and Its Redox Reactions Using Small Molecules for Clinical Advancements in Cancer Therapy
Conclusions
References
119 Cancer Stem Cells: Reactive Oxygen Species-Induced Drug Resistance in Cancer
Introduction
Cancer Stem Cells
Properties of CSCs
Functions of CSCs
Therapy Resistance by CSCs
Reactive Oxygen Species
Cellular Sources of ROS
Cellular Detoxification of ROS
Signaling Pathways Regulated by ROS in Cancer
ROS-Mediated Regulation of the MAPK Pathway
Oxidative Stress Regulation of the PI3K/Akt Pathway
ROS Regulation of the IKK/NF-κB Pathway
Specific Functions of ROS in Cancer
Cancer Metastasis and ROS
Angiogenesis and ROS
ROS in Tumor Cell Proliferation
ROS-Mediated Apoptosis and Cell Survival
ROS and the Mitochondrial Pathway
ROS and the Death Receptor Pathway
ROS and Redox Regulation in CSCs
ROS-Related miRNAs in CSCs
ROS: Drug Resistance
Antioxidant Mechanisms and ROS-Related Markers in CSCs
p38 MAPK Pathway
Aldehyde Dehydrogenases
CD44
CD13
ABCG2 Transporter
ROS and Antioxidants in Cancer Therapy and Prevention
Conclusion
References
120 Reactive Oxygen Species in Oral Squamous Cell Carcinoma Progression and Importance of Stem Cells in Cancer Therapeutics
Introduction
Reactive Oxygen Species (ROS)
ROS in Cancer
Oral Squamous Cell Carcinoma
Impact of ROS in Oral Squamous Cell Carcinoma Initiation and Progression
ROS in Oral Cancer Stem Cells
ROS-Based Anti-cancer Therapy
Cancer Stem Cells in Squamous Cell Carcinoma and Therapy
ROS-Based Stem Cell Therapy in Oral Cancer
Conclusions
References
121 Regulation of ROS in Skin Stem Cells for Cancer Therapeutics
Introduction
Reactive Oxygen Species (ROS)
Skin Cancer: An Overview
Common Treatment Strategies for Skin Cancer
Surgery
Radiation Therapy
Chemotherapy
Immunotherapy
Photodynamic Therapy
Targeted Therapy
Stem Cell
Cancer Stem Cell and Normal Stem Cell
Properties of Cancer Stem Cells
Recent Strategies to Target Cancer Stem Cells
Cancer Stem Cells and Reactive Oxygen Species
Anti-oxidants in Cancer Prevention and Treatment
Manganese Superoxide Dismutase (MnSOD) and Its Clinical Application in Skin Cancer
Skin Cancer Chemoprevention: Role of Nicotinamide
Melatonin and Its Anti-tumor Effects
Phytochemicals in the Treatment of Skin Cancer
Polyphenols Regulating Oxidative Stress in Skin Cancer
Flavonoid (Luteolin) Against Skin Cancer
Photodynamic Therapy (PDT) in Skin Cancer Treatment
Targeting Cancer Stem Cells to Treat Skin Cancer
Stem Cells in Regenerative Medicine
Summary
References
122 Modulation of Reactive Oxygen Species and Cancer Stemness by Catechins
Introduction
Bioavailability and Metabolism of Catechins
Antioxidant Potential of Catechins
Anticancer Properties of Catechins: Targeting Human Cancer Stem Cells
EGCG: The Cancer Stemness Markers and NFKB Signaling Pathway
Green Tea Prevents Cancer
Conclusions
References
123 Mesenchymal Stem Cells
Introduction
Cancer Epidemiology
Current Challenges in Cancer Treatment
Components of the TME
Role of MSCs in the TME
Anticancer Therapeutic Potential of MSCs
Conclusion and Future Perspective
References
124 Induction of Oxidative Stress: A Promising Approach in Female Gynecological Cancer Therapeutic Arsenal
Introduction
OS Involvement in Ovarian Physiology and Malignancy
Redox State in Ovarian Carcinoma
Redox State in Chemoresistant Ovarian Carcinoma
OS-Based Therapies in OC
Antioxidant Role of Metformin in OC Treatment
Endometrial Carcinogenesis and OS Involvement
Antioxidant Role of Metformin in Endometrial Cancer Treatment
Antioxidant Role of Phytochemicals in Endometrial Cancer Treatment
OS Involvement in Cervical Carcinogenesis
Antioxidant Role of Curcumin in Cervical Cancer Treatment
Antioxidant Role of Metformin in Cervical Cancer Treatment
Conclusions
References
125 Iron Vulnerability of Cancer Stem Cells
Introduction
Iron as a Central Player and Essential Target in Cancer Progression
Iron Metabolism in Non-CSCs and CSCs
Iron-Mediated Lipid Peroxidation and Cancer Cell Death
Iron-Mediated Lipid ROS Generation and Ferroptosis in CSCs
Ferroptotic Nexus with Other Forms of Cell Death in Cancer
Ferroptosis and Apoptosis: Synergism or Antagonism
Autophagy Degrades Ferritin to Facilitate Ferroptosis
Small Molecule Lipid ROS Modulators and Their Role in Induction of Ferroptosis in CSCs
Erastin
RSL3
Fin56
FINO2
Salinomycin and Its Derivatives
Molecular and Metabolic Pathways Regulating Iron Mediated Cell Death-Ferroptosis
The Transsulfuration Pathway
The Mevalonate Pathway
SLC7A11 and Its Vital Role in Ferroptosis
Ferroptosis Inhibition by GPX4
Role of ACSL4 in Ferroptosis
Role of FSP-1 in Ferroptosis
Regulation of Ferroptosis by p53
NRF2/NFE2L2-Mediated Ferroptosis
Hippo Signaling Pathway and Its Role in Inhibiting Ferroptosis
Conclusion and Future Perspectives
References
126 Targeting Epithelial-to-Mesenchymal Transition for Breast Cancer Stem Cells Therapeutics
Introduction
Epithelial-to-Mesenchymal Transition (EMT) and Breast Cancer Stem Cells (CSCs)
In Silico Analysis of EMT Genes in Breast CSCs
Preclinical Evaluation of Therapeutics Against EMT in Breast Cancer
Clinical Trials of Candidate Drugs Against EMT in Breast Cancer
Reversing EMT in Metastatic Breast Cancer Stem Cells
Conclusion and Future Perspectives
References
127 ROS Signaling in Brain Tumor
Introduction
Reactive Oxygen Species and Stem Cells
Brain Tumors
Brain Tumor Stem Cells
Current Brain Tumor Treatment Modalities Involving ROS
ROS Modulation in Brain Tumor Stem Cells for Therapeutic Intervention
Future Perspective
References
128 Current Insights to Therapeutic Targets of ROS-Induced Gastric Cancer Stem Cells
Introduction
Classification of Gastric Cancer
Histological Basis
Adenocarcinoma
Lymphoma
Gastrointestinal Stromal Tumor (GIST)
Gastrointestinal Carcinoid Tumor
Other Cancers
Molecular Basis
The Cancer Genome Atlas (TCGA) Subtypes
The Asian Cancer Research Group
Stem Cells in the Stomach
Reactive Oxygen Species in Gastric Cancer
Role of Reactive Oxygen Species and Helicobacter Pylori in Gastric Cancer
Gastric Cancer Stem Cells
Markers of GCSC
ROS and Gastric Cancer Stem Cell
Current GC Treatment and Prospects for Targeting GCSC
Prospects for Gastric Cancer Treatment by Targeting ROS
Conclusion
References
129 Clinical Approaches in Targeting ROS-Induced Cancer
Introduction
Therapies
Drug-Based Therapies
Immunotherapy
Photoimmunotherapy (PIT)
Tumor-Infiltrating Lymphocytes (TIL)
CAR T-Therapy
Monoclonal Antibodies (mAbs)
Photodynamic Therapy (PDT)
Sonodynamic Therapy (SDT)
Hydrogen Gas Therapy
HSP90 Inhibitors
Mn Porphyrins
Vaccines
Hematopoietic Stem Cells (HSC) Therapy
Immunosenescence
Conclusion
References
130 ROS-Induced Cancers
Introduction
Oxidative Stress - Implications of ROS in Cancer
Generation of ROS
Effects of ROS - Two Opposing Actions on Cancer Cells
ROS in Favor of Oncogenesis
ROS Can Destroy Cancer Cells
ROS in Cancer Therapy
Chemotherapy
Radiotherapy
Surgery
Targeting ROS in Glioma and Other Cancers: Implication of Combinatorial Approach
Erythroid 2-Related Factor 2 (Nrf2)
Cannabidiol (CBD)
Deoxy-Podophyllotoxin (DPT)
Bevacizumav
Nanotherapy Is the Best Choice for Targeting ROS in Glioma and Other Cancers
Cerium Oxide Nanoparticles (CNP)
Nanoceria
Conclusion
References
131 An Insight into Targeted Therapy for Ovarian Cancer
Introduction
Targeted Therapies
Homologous Recombination and PARP Inhibitors in OC Therapeutics
VEGF/VEGFR-Mediated Angiogenesis
PI3K/AKT/mTOR Pathway
Cyclin-Dependent Kinases (CDKs)
MAPK Pathway
SRC Family Kinases
Folate Receptor Alpha
p53 Pathway
Immunotherapy
MicroRNA-Based Therapeutics
Combination Therapy
Conclusion
References
Part VI: Nanotechnology-Based Therapeutics of ROS-Induced Cancer
132 The Multifaceted Function of Nanoparticles in Modulating Oxidative Stress in Cancer Therapy
Introduction
Application of Antioxidant Nanoparticles in Therapeutic Approaches
Antioxidants
Nano-antioxidants
Function of Nanoparticles as Antioxidant
Protective Activity of Nanoparticles Against Induced Oxidative Stress in Normal Cells
Mechanism of Nanoparticles to Induce Oxidative Stress and Toxicity in Cancer Cells
Generation of ROS
DNA Damage
Source of Nanomaterials and Their Impact on Cytotoxicity and Oxidative Stress
Metal Nanoparticles
Nonmetal Nanoparticles
Detection of Oxidative Stress in Cancer Cells Through Nanoparticle-Based Sensors
Conclusion
References
133 Selenium Nanoparticle in the Management of Oxidative Stress During Cancer Chemotherapy
Introduction
Cancer and Stages of Carcinogenesis
Insight into the Role of Reactive Oxygen Species in Cancer
Different Aspects of Cancer Chemotherapy
Selenium and Its Efficacy
Development of Nano Selenium for Application in the Field of Cancer
Nano Selenium in Combination with Antineoplastic Drugs for Cancer Therapy
Differently Functionalized/Decorated Nano Selenium with Anticancer Drugs in Cancer Therapy
Organo Diselenide Nano Composite as the Carrier of Cancer Chemotherapeutic Drugs
Conclusion and Future Direction
References
134 Emerging Role of Redox-Active Nanoceria in Cancer Therapeutics via Oxidative Stress
Introduction
Anticancer Activity of CeO2NPs
Colon Cancer
Breast Cancer
Lung Cancer
Cervical Cancer
Ovarian Cancer
Liver Cancer
Skin Cancer
Prostate Cancer
Gastric Cancer
Bone Cancer
Neuroblastoma
Fibrosarcoma
Drug Delivery Application of CeO2NPs
Conclusion and Future Perspectives
References
135 Nanotechnology in ROS-induced Cancer Therapy
Introduction
What Is Reactive Oxygen Species
Promotion of Cancer by Oxidative Stress and Expose the Achilles Heel
ROS: A Double-edged Sword
Role of ROS in Cancer Cell Killing
Cellular Apoptosis and ROS
Autophagy and ROS
Anticancer Therapy and ROS
Antioxidant System Inhibition Within Cancerous Cells
ROS Production in Cancerous Cells
miRNAs and ROS
ROS-mediated Cancer Cell Killing via Nanoparticles
Antioxidant-mediated Cancer Cell Killing Through Dietary Phytochemicals
Role of Different Nanomaterials (NPs) in Cancer Treatment
Organic Nanomaterials in Cancer Therapies
Polymeric Micelles (PMs)
Polymeric Nanoparticles
Liposome
Dendrimers
Inorganic Nanoparticle
Silica Nanoparticles
Nanographene
Gold Nanoparticles (AuNPs)
Quantum Dots (QDs)
Conclusion and Future Perspective
References
136 Nanotechnology-Based ROS-Triggered Therapeutic Strategies in Multiple Cancer
Introduction
Reactive Oxygen Species
Oxidative Stress: ``A Necessary Evil´´ in Cancer Pathogenesis
Nanoparticle-Mediated ROS Generation in Cancer Therapy
ROS-Inducing Strategy of NPs
Photodynamic Therapy
Sonodynamic Therapy
Microdynamic Therapy
Ferroptotic Therapy
Gas Therapy
Reports on NP-Mediated Enhanced Target Specificity and Reduction in Side Effects of Different Sensitizers
ROS-Mediated Tumor Cytotoxicity by Nanoparticles
Metal and Metal Oxide NPs
Silver NPs
Magnetic NPs
Selenium NPs
Cadmium Quantum Dots
Zinc Oxide NPs
TiO2 NPs
Nickel Oxide
Cerium Oxide NPs
Some Other NPs
Graphene Oxide NPs
Protein NPs
Limitations Associated with Metal-Metal Oxide NPs in Cancer Therapy
Nanocarriers Used in Commercially Available ROS Generating Chemotherapeutics
Conclusion
References
137 Nanotechnology in Cancer Diagnosis and Therapy
Introduction
Nanotechnology in Drug Delivery and Cancer Therapy
General Means of Nanoparticle-Based Targeted Drug Delivery
Passive and Active Targeting
Stimuli-Responsive Drug Targeting and Triggered Release System
Nano-formulations in Cancer Therapy
Nanotechnology in Cancer Immunotherapy
Nanotechnology in Cancer Diagnosis
Challenges and Future Prospects
Conclusion
References
138 Biogenic Nanomaterials Derived ROS for Cancer Therapy
Introduction
Biogenic Nanoparticles
Biogenic Synthesis of Nanoparticles
Reactive Oxygen Species Based Cancer Therapy
Redox Homeostasis by Nanoparticles
Biogenic Nanoparticles for Redox-Based Cancer Immunotherapy
PLGA Biogenic Nanoparticles
Liposomes Biogenic Nanoparticles
Cerium Oxide Nanoparticles
Paramagnetic Iron Oxide Nanoparticles
Gold Nanoparticles
Iron Oxide Nanoparticles
Carbon Nanoparticles
Nanoparticles Induced ROS Generation to Alter Biological Functions
Nanoparticles Induced DNA Damage
ROS Mediated Combinatorial Nanoparticle for Anticancer Therapy
Conclusions
References
139 Emerging Nano-selenium: An insight to Its Current Status and Potentials in ROS-Induced Cancer Prevention and Therapy
Introduction
Reactive Oxygen Species and Carcinogenesis
Selenium Nanoparticles (Se-NPs) and Its Importance
Immense Role of Selenoproteins in the Pharmacological Activity of Se-NPs
Se-NPs as Prooxidant
Se-NPs as Antioxidants
Se-NPs as Anticarcinogenic
Se-NPS as Antimicrobial Agent
Conclusion
References
140 Oxidative Stress-Dependent Anticancer Potentiality of Nanotherapeutic Zinc Oxide
Introduction
Importance of Nanotechnology in Biomedical Research
Reason for Considering ZnO NPs in Anticancer Therapy
Synthesis Techniques of ZnO NPs
Chemical Coprecipitation
Sol-Gel Method
Solution-Free Mechanochemical Method
Ultrasonication
Solid-State Pyrolytic Method
Biological Methods
Brief Insight into the Mechanism of ZnO NP Internalization
Mechanism of ZnO NP-Imposed Anticancer Effects
ZnO NPs and Apoptosis
Zinc-Driven Altered Protein Activity
ROS Generation and Oxidative Stress Induction
ROS-Induced DNA Damage and Subsequent Apoptosis
ZnO NPs and Autophagy
ZnO NPs and Inflammation
ZnO NPs as Vehicle of Chemotherapeutic Drug Delivery
The Role of ZnO NPs in Drug Delivery System
Conclusion
References
141 Polymeric Nanoparticle-Encapsulated Curcumin: A Preventive Strategy in ROS-Induced Carcinogenesis
Introduction
Role of Reactive Oxygen Species (ROS) on Carcinogenesis
Polymeric Nanoparticle-Encapsulated Curcumin and Its Importance
Polymeric Nanoparticle-Encapsulated Curcumin as Antioxidant
Polymeric Nanoparticle-Encapsulated Curcumin as Antioxidant and as Anticarcinogenic
Polymeric Nanoparticle-Encapsulated Curcumin as Antioxidant and as Antimicrobial Agent
Conclusion
References
142 EPR-Selective Biodegradable Polymer-Based Nanoparticles for Modulating ROS in the Management of Cervical Cancer
Introduction
Main Text
Introduction
Cervical Cancer vs ROS
Role of ROS in Cervical Cancer Progression
Role of ROS in Cervical Cancer Therapy Resistance
Role of ROS in Cancer Cell Destruction
Biodegradable Polymer-Based Nanoparticles for Enhanced Permeability and Retention
Polymers as Targeting Moieties
Polymers as Drug Delivery Carriers
Relation Between Biodegradable Polymers with ROS
ROS-Based Solubility Switch
ROS-Based Bond Cleavage
Other ROS-Based Mechanism
ROS-Regulated Signal Pathway and Oxidative Stress in Cancer Promotion
Nuclear Factor-Kappa B Signaling Pathway
MAPK/ERK Pathway
Oxidative Stress Regulation of the PI3K/AKT Pathway
EGFR/VEGFR Signaling Pathway
Apoptotic Signaling Pathways
Biodegradable Polymer in Modulation of ROS
Thermo-responsive Polymer
pH-Responsive Polymers
ROS-Responsive Polymers
H2O2-Responsive Polymer
Light-Triggered Polymers
Prospects
Conclusion
References
143 Graphene-Based Nanomaterials for ROS-Mediated Cancer Therapeutics
Introduction
Background of Graphene-Based Nanomaterials
Historical Background
Synthesis
Graphene Nanomaterials
Reactive Oxygen Species
Background of ROS
Sources of ROS
Molecular Targets of ROS
Role of ROS in Cancer Therapeutics
Therapeutic Applications of Graphene Based Nanomaterials
Graphene Oxide (GO)
Reduced Graphene Oxide (rGO)
Graphene Quantum Dots
Graphene Scaffolds
Mechanism of Action of Graphene Based Nanomaterials
Toxicity of Graphene Based Nanomaterials
Challenges and Future Perspectives
Conclusion
References
144 Bio-inspired Protein-Based Nanoparticles in Cancer Therapy
Introduction
Cancer Therapy
Synthesis of Protein-Based Nanoparticles
Chemical Methods
Emulsion
Coacervation
Physical Methods
Nano-Spray Drying
Electro Spray
Self-Assembly Methods
Self-Assembly
Desolvation
Protein Nanoparticles for Cancer Therapy
Albumin-Based Nanoparticles
Gelatin-Based Nanoparticles
Transferrin-Based Nanoparticles
Ferritin-Based Nanoparticles
Gliadin-Based Nanoparticles
Silk Fibroin-Based Nanoparticles
Zein Based Nanoparicles
Lipoprotein-Based Nanoparticles
Other Proteins-Based Nanoparticles
Conclusion and Future Perspectives
References
145 ROS-Responsive Bioconjugate Nanoparticles in Cancer Treatment
Introduction
ROS, Fenton Reaction, and Cancer
Tumor Targeting Strategies
Targeting Cancer Tumors Based on Their Distinguished Pathophysiology
Targeting Cancer Tumors Based on the Special Properties of NDDS
Bioconjugation Strategies
ROS Induction for Cancer Treatment Using Bioconjugates
ROS-Mediated Drug Release via Bioconjugates
Thioketal Linkers
Arylboronic Esters Linkers
Diselenide Linkers
Mesoporous System
Conclusion and Future Perspectives
References
146 Harnessing Microenvironment Variation for Nanotechnology-Based Therapeutics of ROS-Induced Cancer
Introduction
Section 1: ROS in Mediating Drug Delivery Using ROS-Responsive Drug Delivery
Nanocarriers with ROS-Induced Solubility Change
Nanocarriers with ROS-Induced Cleavage
Section 2: Effect of Tumor Microenvironment on ROS-Responsive DDS
Normalization of High Interstitial Fluid Pressure (IFP)
Reduction of the Pericyte Coverage
Reducing the Extracellular Matrix Components
Modulating Tumor Vascularization
Tumor-Associated Fibroblast (TAF) Depletion
Conclusion and Future Perspective
References
147 Experimental Animal Models to Evaluate the Therapeutic Efficacy of Nanoformulations Against Cancer
Introduction
Drug Design and Formulation
Cancer
Nanotechnology for Cancer Management
Nanoparticles as Drug Delivery Systems in Cancer Treatment
Nanoparticles as Diagnostic Systems in Cancer Treatment
Biopolymers
Biopolymer Nanoparticle Preparation
Biopolymer Nanoparticle Biomedical Applications
Biopolymers Carrying Anticancer Drugs
Biopolymers and Antioxidant Property
Experimental Animal Models
Small Animal Models for Understanding the Efficacy of Nanocarriers
Large Animal Models for Understanding the Efficacy of Nanocarriers
Xenograft Experimental Models for Understanding the Efficacy of Nanocarriers
Genetically Engineered Models for Understanding the Efficacy of Nanocarriers
Chemically Induced Animal Models for Understanding the Efficacy of Nanocarriers
Zebrafish Model for Understanding the Efficacy of Nanocarriers
Cell Line-Induced Cancer Model for Understanding the Efficacy of Nanocarriers
Drosophila Model for Understanding the Efficacy of Nanocarriers
Conclusion and Way Forward
References
148 Nanotechnologies in Oncology
Introduction
Cancer
Conventional Treatments
Multidrug Resistance
Nanotechnologies in Oncology
Nano-oncology
How Nanotechnology Can Improve Cancer Treatment
Active vs Passive Delivery
Drug Release and Targeting
Diagnostics (Early Detection)
Types of Nanoparticles Used in Nano-oncology
Inorganic/Metallic Nanoparticles
Silver Nanoparticles
Gold Nanoparticles (Au NPs)
Magnetic Nanoparticles
Platinum Nanoparticles (Pt NPs)
Quantum Dots (QDs)
Carbon Nanotubes (CNTs)
Organic Nanoparticles
Liposomes
Polymers
Micelles
Dendrimers
Hydrogels
Biological Nanoparticles
Nanobodies (NBs)
Protein-Drug Conjugated NPs
Extracellular Vesicles (EVs)
Recent Developments in Nano-oncology
Challenges and Future Prospects
Regulatory Issues
Physiochemical Characterization
Toxicology
Large-Scale Production
Conclusions
References
149 A Detailed Overview of ROS-Modulating Approaches in Cancer Treatment
Background
Role of Reactive Oxygen Species (ROS) in Normal Healthy and Cancer Cells
Role of ROS in Normal Cells
Reactive Oxygen Species Role in Cancer Cells
Cancer Treatment: ROS-Modulated Therapeutic Approaches
ROS Scavenging Anticancer Approaches (Antioxidant Therapy)
ROS-Promoting Therapy (Prooxidant Therapy)
Need for Targeted Nanosystem Approach Delivery for Prooxidant Therapy
Nanoparticles as Passive Agent: Drug Carrier
Nanoparticles as Active Agent: Drug Carrier Cum PDT Agent
Conclusion
References
150 Nanotechnology-Based Therapeutics in ROS-Induced Cancer
Introduction
Oxidative Stress and Carcinogenesis
Advantages of Nanomedicine
Nanoparticles Targeting Mechanisms
Nanoparticles-Induced Oxidative Stress
Nanoparticles as Drug Delivery System
Redox-Responsive Systems
ROS- and GSH-Responsive Nanoparticles
Regulating and Manipulating Antioxidants
Organic NPs
Inorganic NPs
Hybrid NPs
Targets of ROS-Induced Cancer Therapy
Internal Stimuli Targets
External Stimuli Targets
Temperature Stimuli-Responsive Systems
Photo-/Light-Responsive Systems
Magnetic-Responsive Systems
Ultrasound-Responsive Systems
Conclusions
References
151 Recent Developments in ROS-Based Nanotherapeutic Modalities in Preclinical Cancer Treatment
Introduction
ROS-Based Cancer Nanotherapeutics
Photodynamic Therapy (PDT)
Sonodynamic Therapy (SDT)
Radiation Therapy (RT)
Chemodynamic Therapy (CDT)
Controlled Drug Release (CDR)
Synergistic Therapy
PDT-Based Synergistic Therapy
SDT-Based Synergistic Therapy
RT-Based Synergistic Therapy
CDT-Based Synergistic Therapy
Conclusions and Outlook
References
152 Free Radical Chemistry of Carotenoids and Oxidative Stress Physiology of Cancer
Introduction
Structural Properties of Carotenoids
Chemical Properties of the Major Carotenoids
Carotenoids as Antioxidants
Carotenoids as Anticancer Molecules in the Perspective of Free Radical Chemistry
Carotenoids and Their Synergism on Oxidative Stress-Mediated Apoptosis
Role of Carotenoid Oxidation Products/Isomers/Metabolites in Cancer Cells
Chemical Biology Approach Through Synthetic Chemistry
Deciphering the Mechanism of Action
Conclusion
References
153 Targeting Redox Homeostasis in Tumor Cells Using Nanoparticles
Introduction
Biology of ROS Productions and Its Outcome
Importance of Redox Homeostasis in Cancer Therapy
Nanoparticles for Mediating Redox Imbalance and ROS Generation in Cancer
Inorganic Nanoparticles for Altered Redox Homeostasis
Organic Polymer Nanoparticles and Carbon Nanostructures for Redox Stress
NP Mediated Photodynamic Therapy-Induced ROS Production
Mechanisms of NPs Mediated ROS Toxicity and Disruption of Redox Homeostasis in Cancer Cell
Conclusion and Future Direction
References
154 In Silico Analysis of Oxidative Stress Gene Expression Profile and Biomarker Detection
Introduction
Anti-oxidative Stress Gene Profiling
Thioredoxin Pathway
Glutathione Pathway
BioProfiling.de Portal
Biomarker in Oxidative Stress
miRNA
miRNA Target Identification Tools
TargetScan
DIANA-microT-CDS
PicTar Algorithm
miRanda Algorithm
RNAhybrid Algorithm
DNA Methylation Analysis
Bioinformatics Tools for Detection of DNA Methylation Data
DNA Methylation Databases
CpG Islands Detection Tools
Conclusion
Bioinformatics Analysis
Case Study 1 (Fig. 1)
Case Study 2 (Fig. 2)
References
155 Nanomedicines for Tumor-Associated Macrophages
Introduction
Therapeutic Modalities to Target TAMs
Developing Nanomedicines Against TAMs
TAM-Specific Nanocarriers
Polymeric Nanoparticles
Liposomal Nanoparticles
Inorganic Nanoparticles
Carbon-Based Nanoparticles
Functionalization of Nanocarriers to Target TAMs
Carbohydrates as Targeting Motifs
Proteins/Peptides as Targeting Motifs
Effector Molecules Conjugated to Nanocarriers
Limitations of TAM-Specific Nanotherapy and Its Future
Conclusion
References
156 Synthetic Migrastatic: A New Class of Anticancer Drug
Introduction
Metastasis Modality
Main Text
Current Therapeutic Regime and Problems
Migrastatics: A New Class of Drugs
Potential Targets for Migrastatic Compounds
Cytoskeletal Proteins
Actin-Related Proteins
Focal Adhesion Complex Protein
Enzymes and Signaling Protein
Migration-Specific Small GTPase
Potential Migrastatic Compounds
Myosin Inhibitor
Arp2/3 Inhibitor
Tropomycin Inhibitor
Inhibitors of Rho-Kinase (ROCK)
Actin Filament-Related Inhibitor
MLCK Inhibitor
Protein Enzyme Inhibitor
Probable Problems with Migrastatic Candidates as Anticancer Drugs
Future Perspective and Conclusion
References
157 Targeting Reactive Oxygen Species (ROS) for Cancer Therapy
Introduction
How ROS and Oxidative Stress Are Interlinked?
ROS Signaling in Cancer Biology
How ROS Severe the Metastasis?
ROS as a Cancer Therapy
How Low ROS Prevent Cancer Progression?
Toxic ROS as Therapy for Cancer Treatments
Mitochondria: The Novel Targets for ROS in Cancer Treatment
Crosstalk Between Autophagy and Apoptosis-Targeting ROS
Mathematical Modeling for Selecting Appropriate ROS Therapy
ROS Detection in Cancer Treatments
Conclusion
References
Part VII: Bioinformatics and System Biology Approach for Targeting ROS in Cancer Therapy
158 Elucidation of Possible Role of Heat Shock Protein as Potent Therapeutic Agent in ROS-Mediated Cancer and Its Assessment T...
Introduction
Origin of ROS
ROS-Regulated Signal Pathways in Cancer
ROS in Advancement of Tumor Cells
Personification of HSP in Cancer Ontogeny
Role of HSP27 in Cancer Progression
Functional Activity of HSP60 in Cancer Prognosis
Execution of HSP70 in Cancer Augmentation
Role of HSP90 in Cancer Advancement
Function of HSF1 in Cancer Prognosis
Pointing HSP40
Marking HSP60
Targeting HSP70
Targeting HSP90 in Cancer
The Computational Approach: An In Silico Methodology
High-Throughput Data Analysis and Bibliographic Analysis
Differential Gene Expression and Correlation Analysis
Structural Analysis by Targeting Small Heat Shock Proteins as Potential Candidates in Therapeutic Studies
Network and Pathway Enrichment Analysis
Conclusion
References
159 An Overview of In Silico Drug Discovery with Emphasis on Cancer
Introduction
Overview of Different Computational Methods
Quantitative Structure Activity Relationship (QSAR)
Classification of the QSAR Methods
Limitations of Classical Quantitative Structure Activity Relationship
Three-Dimensional Quantitative Structure Activity Relationship
Overview of ROS-Induced Cancer
Application of Quantitative Structure Activity Relationship in Drug Development
A Few Success Stories
Conclusion
References
160 Application of Bioinformatics Databases in the Study of Oxidative Stress Related Cancers
Introduction
Essential Aspects of Reactive Oxygen Species (ROS)
Interrelation Between Reactive Oxygen Species (ROS) and Cancer
Anticancer Strategies
Importance of Bioinformatics
Biological Databases
RedoxiBase: A Database for ROS Homeostasis Regulated Proteins (https://peroxibase.toulouse.inra.fr)
COSMIC: Catalogue of Somatic Mutations in Cancer (https://cancer.sanger.ac.uk)
ONCOMINE: A Cancer Microarray Database (https://www.oncomine.org)
miRCancer: A MicroRNA-Cancer Association Database (http://mircancer.ecu.edu)
Lnc2Cancer: A Manually Curated Database of Experimentally Supported lncRNAs Associated with Various Human Cancers (http://bio-...
The Cancer Genome Atlas (http://cancergenome.nih.gov/)
canSAR (https://cansarblack.icr.ac.uk/)
MethyCancer (http://methycancer.psych.ac.cn/)
miRCancer (http://mircancer.ecu.edu/)
Network of Cancer Genes (http://ncg.kcl.ac.uk/)
Biological Databases, Bioinformatics, and Their Roles in Cancer Therapy
Conclusion
References
161 Emerging Scope of Computer-Aided Drug Design in Targeting ROS in Cancer Therapy
Introduction
ROS-Based Targets/Pathways for Screening
Application of Modeling Methods for ROS
ROS In Vitro Estimation
Modeling Approaches and Classification
Applicability of In Silico Modeling to Study ROS Biology
Software Tools for Modeling ROS Biology
Limitations of Mathematical Modeling
Integration of ROS Modeling with Omics Data
Omics Databases
Computer-Aided Drug Design: A Pipeline for Converting Structure Biology Data into the Forecasting of Drug Therapies
Conclusion
References
162 ROS Modulatory Role of HDAC Inhibitors in Cancer Cells
Introduction
HDAC Inhibitors and ROS Production
HDAC Inhibitors and Protein Quality Control Systems
Molecular Chaperons
Ubiquitin Proteasome System
Autophagy
Endogenous ROS Activation
Thioredoxin Role in ROS Regulation
Glutathione Role in Antioxidation
Reactive Oxygen Species: Types, Source, and Detoxification
ROS in Normal, Cancer, and Cancer Stem Cells
ROS Production
ROS in Cancer and Role of Signaling Pathways
Foxo Protein Signaling in ROS Generation in Lung Cancer
ROS-Dependent Gene Expression in Cancer Cells
Anti-oxidative Stress (AOS) Genes
HDAC Inhibition and ROS
HDAC Inhibitor and YB1 Relation in ROS Production
HDAC Inhibitors and ROS-Mediated Effects on Cancer Cells
GBM vs. ROS
HDAC Inhibitors in Bladder Cancer
Resistance Against HDAC Inhibitors in Gastric Cancer
HDAC Inhibitors in Rhabdomyosarcoma
HDAC Inhibitors and Autophagy
Systemic Approaches
System Biology Approach on Regulation of Molecular Pathways by HDAC Inhibitors in Cancer
Computational Approach in Drug Discovery
Potential Application of HDAC Inhibitors in Inducing Apoptosis
Conclusions and Future Directions
References
163 Therapeutic Potential of Modulating Oxidative DNA Damage in Breast Cancer
Introduction
Role of Estrogens in Oxidative DNA Damage
Oxidative Stress-Induced Chemoresistance in Breast Cancer
Therapeutic Potential of Natural Products as Oxidative Stress Modulators
Therapeutic Potential of Nanoparticles as Oxidative Stress Modulators
Drug Repurposing
References
164 Systems Biology and Bioinformatics Approaches Unraveling the Therapeutic Potential of Novel Drugs in Counteracting the Oxi...
Bioinformatics Analysis of Differentially Expressed Genes
Lipidomics Analysis Using Artificial Neural Networks
Zinc Chelation Therapy
Modulating Xenobiotic Metabolism
Modulating NOTCH Signaling
Targeting Arachidonic Acid Pathway
Inducing Mitochondrial Stress
Androgen Deprivation Therapy
References
Part VIII: Other Aspects of Therapeutics of ROS-Induced Cancer
165 Some Aspects of Oxidative Stress–Induced Prostate Cancer Therapy
Introduction
Prostate Cancer, Enzymatic Antioxidants, and Associated Biomolecules
Prostate Cancer and Nonenzymatic Antioxidants
Prostate Cancer and Noncoding RNA (ncRNAs)
Prostate Cancer and MicroRNA
Prostate Cancer and Inflammatory Oxidative Stress
Oxidative Stress and DNA Damage in Prostatic Hyperplasia
Genetic Modulation in PCa Cells by ROS
GST Superfamily and PCa
AR Signaling, Hormone Deprivation, and CRPC Outgrowth
Androgen Deprivation Therapy (ADT) and CRPC Progression
Interleukin-6 in Redox-Signaling Amplification in CRPC Cells
Therapeutic Efficacy of Nrf2 Against CRPC Progression
Role of NF-κB on AR Function
Transcription Factors-Induced AR Expression and CRPC Development
Conclusion and Future Perspectives
References
166 Reactive Oxygen Species in Glioma
Introduction
Basic Biology of Glioma
Current Standard of Therapy
Oxidative Stress in Brain and CNS
Oxidative Stress and Tumor-Associated Inflammations
Oxidative Stress and Immune Cell Functionality
ROS and Energy Homeostasis in Cancer
Oxidative Stress and Circadian Rhythms
Oxidative Stress and Therapy Resistance
Conclusion and Future Direction
References
167 Genetic Factors Contributing ROS-Driven Chemotherapy and Drug Resistance in Cancer
Introduction
Types of Chemotherapeutic Drugs
The Role of ROS in Tumor Development
ROS Plays Critical Role in Chemotherapeutic Drug Resistance
Most Anticancer Drugs Use ROS to Kill Cancer Cells Through Common Molecular Pathways
Identification of Genetic Factors Involved in Chemotherapeutic Drug Resistance
Whole Genome Approach
Identifying Genes for Chemotherapy Using Microarray
Polymorphic Variants in ROS Modulatory Genes Play a Critical Role in Chemotherapy
Role of DPYD Gene in Chemotherapy
Implications
References
168 Metabolic Oxidative Stress
Introduction
Metabolic Pathways in Cancer
Metabolic Reprogramming: A Major Hallmark of Cancer
Glucose
Glutamine
Lipid Scavenging and Fatty Acid Oxidation
NADPH
Relationship Between High Metabolic Rate and ROS Generation
p53 and ROS Metabolism
FOXOs and ROS
Role of ROS in Cancer Progression
Role in Angiogenesis
ROS in Metastasis
Metabolic Therapy: Evolving Role of Mitochondria in Metabolism
Ketogenic Metabolic Therapy (KMT)
Conclusions
References
169 A CRISPR-Cas9-Based Therapeutics in Oxidative Stress-Induced Cancer
Introduction
ROS-Induced Carcinogenesis
ROS-Induced Genetic Instability
ROS-Induced Alteration of Signaling Pathways
CRISPR-Cas9 in Cancer Research
Application of CRISPR-Cas9 in Cancer Diagnosis
Application of CRISPR-Cas9 in Cancer Therapeutics
Application of CRISPR-Cas9 in the Generation of Cancer Models
Role of CRISPR-Cas9 in Epigenetic Modifications in Oxidative Stress-Induced Cancer
Limitations of the CRISPR-Cas9 in Cancer Therapeutics
Concluding Remarks
References
170 Molecular Mechanism of Oxidative Stress in Cancer and Its Therapeutics
Introduction
Production of ROS and Status of Endogenous Antioxidant in Tumorigenesis
Association Between Oxidative Stress and Carcinogenesis
Signaling Pathways Involved in ROS-Mediated Tumorigenesis
ROS- and NF-kB-Mediated Tumorigenesis
ROS- and MAPK/ERK -Mediated Tumorigenesis
ROS- and Akt/PI3K/mTOR-Mediated Tumorigenesis
ROS- and Tumor-Suppressive Genes
ROS and Angiogenesis
ROS and Tumor Initiation and Proliferation
ROS and Tumor Survival and Invasion
ROS and miRNA
ROS, Mitochondrial Dysfunction, and Tumorigenesis
Antioxidant and Prooxidant: Dichotomous Approach Toward ROS in Tumorigenesis
Conclusion
References
171 Pro-apoptotic Effects of Dietary Flavonoids in Oxidative Stress-Induced Cancer
Introduction
Oxidative Stress and Reactive Oxygen Species
Regulation of ROS at Enzymatic Level
Regulation of ROS at Molecular Levels
Apoptosis: Pathways and Proteins Involved
Intrinsic or Mitochondria-Dependent Pathway
Extrinsic or Death Receptor-Induced Pathway
Dietary Flavonoids with Pro-apoptotic Effect Against Experimental Cancers
Quercetin
Morin
Epigallocatechin-3-Gallate
Genistein
Daidzein
Apigenin
Luteolin
Myricetin
Hesperidin
Conclusion
References
172 Redox Signaling
Introduction
Tumor Microenvironment (TME)
Redox Microenvironment in Cancer Cell (RME)
Redox Signaling and Cancer Cell Cycle
Redox Signaling and Metabolic Rewiring in TME
Redox-Mediated Cancer Progression
Redox Signaling and Chemoresistance in Cancer
Mechanisms of Chemoresistance (Table 5)
Oxidative Stress-Mediated Activation of Autophagy
ROS in ER Stress-Mediated Autophagy
ROS and Cell Cycle Arrest
Involvement of Epithelial-Mesenchymal Transition (EMT) and Cancer Stem-like Cells (CSC) in Chemoresistance
Redox Balance and Chemoresistance
Conclusion
References
173 Mechanistic and Therapeutic Crosstalk of Lipid Peroxidation in Oxidative Stress and Breast Cancer
Introduction
Metabolic Adaptation of Breast Cancer Cell
Epigenetics
Glycolytic Shift
Lipid Peroxidation and Underlying Mechanism
Oxidative Stress in Angiogenesis and Apoptosis
Inflammation
Angiogenesis
Redox Homeostasis
Apoptosis
Free Radicals and Antioxidant Dual Component
ROS, RNS, and RCS
Hereditary Crosstalk of Hypoxia
Tumor Microenvironment
Role of TAMs
PHD2 and HIF1-α
Targeted Therapy
Conclusion and Future Perspective
Challenges in the Area
References
174 Therapeutic Implication of Oxidative Stress Regulators in Drug-Resistant Cancers
Introduction
Therapeutic Implication of Oxidative Stress Regulators in Drug-Resistant Cancers
Mitochondrial Respiratory Chain Complex Regulators
NOX Regulators
GSH Regulators
γ-GCS Regulators
GPx Regulators
GST Regulators
SLC7A11 Regulators
TrxR Regulators
SOD Regulators
HO-1 Regulators
Nrf2- Keap1 Regulators
UCP2 Regulators
Prxs Regulators
Other Key Proteins in Regulating Redox Homeostasis
Other Small-Molecule Oxidative Stress Regulators
Conclusion and Future Perspectives
References
175 Y-Box-Binding Protein-1
Introduction
YB-1 Structure and RNA/DNA Interactions
Role of YB-1 in Oxidative Stress and Cancer Therapy
YB-1 and Cancer
YB-1 and Different Signaling Axis
YB-1 and Ras-Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Signaling
Inhibition of YB-1 and AKT Signaling
YB-1 and HER2 Axis
YB-1-Based Virotherapy for Cancer Treatment
YB-1 and Immunotherapy for Cancer Treatment
Conclusion
References
176 Microbe-Induced Oxidative Stress in Cancer Development and Efficacy of Probiotics as Therapeutics in Preventing Its Onset ...
Introduction
Bacteria-Induced Oxidative Stress Promotes Cancer Development
Oxidative Stress in the Digestive System
Oral Carcinogenesis
Oxidative Stress in the Gastrointestinal Tract
Oxidative Stress in the Colon
Oxidative Stress in the Reproductive System
Oxidative Stress in the Respiratory System
Bacterial Toxins Induced Cancer Development
DNA-Damaging Toxins
Colibactin
Cytolethal Distending Toxin
Cell-Signaling-Disrupting Toxins
Cytotoxin-Associated Gene A (CagA) and Vacuolating Cytotoxin A (VacA)
Cytotoxic Necrotizing Factor 1
Bacteroides fragilis Toxin
Staphylococcal Enterotoxins
Avirulence Protein A
FadA
The Role of Protozoa in Cancer Development
Toxoplasma gondii
Cryptosporidium parvum
Trichomonas vaginalis
Plasmodium falciparum and Burkitt Lymphoma
Entamoeba histolytica
Blastocystis hominis
Giardia lamblia
Therapeutic Roles of Probiotics in Cancer Treatment and Prevention
Production of Antimicrobial Substances
Improvement of Intestinal Barrier
Modulation of the Immune System
Antioxidant Properties of Probiotics
Antiproliferative Activity of Probiotics
Future Perspective
References
177 Role of Forkhead Box Proteins in Regulating Epithelial-Mesenchymal Transition in Breast Cancer
Introduction
Breast Cancer: The Unconquered Human Malady
Breast Cancer Types and Diagnosis
Pathology of Breast Cancer and Staging
Estrogen Signaling in Breast Cancer
ER Stress-Manifested X-Box Protein 1-Binding Protein in Cancer
The Discovery, Functions, and Significance of X-Box-Binding Protein in Breast Carcinogenesis
Role of FOXO Transcription Factor as Regulators of Epithelial-Mesenchymal Transition
Forkhead Box M1 and Malignancy: The Notorious Nexus
Normal Physiological Roles and Functions of FOXO Family
Cancer-Preventive Effects of FOXO
Role of FOXO Proteins and X-Box-Binding Proteins on Oxidative Stress
FOXO Proteins, X-Box-Binding Proteins and Apoptosis
miRNA-Mediated Control of FOXO Expression in Cancer
FOXOs and Autophagy
The PI3K/Akt Signaling and FOXO Connection
FOXO and Angiogenesis in Cancer
FOXO and XBP1 as Targets in Breast Cancer Therapy
Future Prospective
Conclusion
References
178 Targeting Mitochondria as a Novel Disease-Modifying Therapeutic Strategy in Cancer
Introduction
The Chemistry and Biology of ROS
ROS: A Family of Reactive Oxygen Molecules
Role of ROS in Cancer Progression
Consequences of Oxidative Stress in Cancer
ROS as an Initiator of Cancer
ROS and Tumor Microenvironment
Role of Oxidative Stress in Cancer Stem Cells
ROS, Mitochondrial Fission/Fusion, and Cancer
Therapeutic Potential of Oxidative Stress Pathways
Inhibitors of Electron Transport Chain Induces ROS Production in Tumor Cells
Inhibition of Antioxidant Enzyme System by Natural Products
Mitochondrial Fission and Fusion for Therapy
Combining Oxidative Stress Enhancers with Immunotherapy
Conclusion and Future Direction
References
179 Pathogenesis of Oxidative Stress in Lung Cancer and Its Therapeutic Aspects
Introduction
Pathogenesis of Lung Cancer
Domestic Exposure
Occupational Exposure
Infections
Environmental Smoke
Smoking Tobacco
Substances Causing Oxidative Stress
Cigarette Smoking and Oxidants
Oxidants and Silica (SiO2)
Induced Particle Oxidants
Asbestos and Oxidants
The Role of Oxidants in Domestic Cooking
Pathophysiology of Oxidants
Oxidative Stress and Inflammation
Oxidative Stress Induces DNA Alteration and Lung Cancer
Degeneration of Lipid and Protein
Imbalance of Oxidant/Antioxidant
Role of Antioxidants in Lung Cancer Chemoprevention
Antioxidant and Treatment of Lung Cancer
Conclusion
References
180 Modulators of ROS/NF-κB Signaling in Cancer Therapy
Introduction
NF-κB Signaling Pathway
ROS/NF-κB Signaling
Modulators f ROS/NF-κB Signaling
Phenols
Alkaloids
Terpenoids
Steroids and Saponins
Polyketides
Conclusions
References
181 Targeting Tumors Through Enhancers of Oxidative Stress
Introduction
Etiology of Cancer
Tobacco
Environmental Carcinogens
Diet, Obesity, and Physical Activity
Mitochondrion Structural Components and Functions
Structure of Mitochondria
Mitochondrial DNA
Functions of Mitochondria
Electron Transport Chain in Mitochondria
Reactive Oxygen Species in Mitochondria
Mitochondrial Dysfunction
Therapeutic Targets in Cancer Pathology
Mitochondrial Medicine in Cancer
Bioenergetic Therapy in Cancer
Conclusion and Future Perspective
References
182 Proteomics and Metabolomics in Cancer Diagnosis and Therapy
Introduction
Cancer Proteomics
Proteomic Workflow
Proteomics Platforms
MS-Based Proteomic Approaches in Cancer
Electrospray Ionization (ESI) and Matrix-Assisted Laser Desorption/Ionization (MALDI)
SELDI-TOF
QUEST-MS
SPR-MS
Chromatography Coupled with MS
Non-MS-Based Proteomic Approaches in Cancer Biology
Antibody-Based Platform
Immunosensors Based on Lateral Flow Assay (LFA)
Tissue Micro Array (TMA)
Enzyme-linked Immunosorbent Assay (ELISA)
Antibody Array
Reverse-Phase Protein Array (RPPA)
Single-Cell Proteomics in Cancer
Cancer Metabolomics
Metabolomics Workflow
Metabolomics Analytical Platforms
NMR
MS
GC-MS
LC-MS
Supercritical Fluid Chromatography (SFC)
Capillary Electrophoresis (CE)
Ion Mobility Spectrometry (IMS)
DI-MS
MALDI-MS
Direct Analysis in Real-Time (DART)-MS
Mass Spectrometry Imaging (MSI)
Challenges and Opportunities
Conclusions
References
183 Oxidative Stress-Induced Autophagy
Introduction
Autophagy Machinery
The Core Pathway of Mammalian Autophagy
Molecular Mechanism of Autophagy
Initiation
Nucleation
Elongation
Maturation/ Fusion with Lysosomes
Autophagy as an Adaptive Metabolic Response
Intracellular Quality Control by Nonselective and Selective Autophagy
Autophagy in Health and Disease
CNS
Diabetes
Autophagy and Inflammation
Crohn´s Disease
Kidney
Cardiovascular Diseases
ROS and Autophagy
Autophagy and Tumorigenesis
Conclusion
References
184 Antioxidant Supplementation
Introduction (Length Depends on the Topic Describing Importance of Subject and Content)
Main Text
Antioxidant Supplementation: Paradoxical Role in Cancer Therapeutics
Introduction
Reactive Oxygen Species
ROS Generation and its Regulations
Role of ROS as Signaling Molecule
Notch Pathway
MAPK Pathway
NFkB Pathway
ROS-Driven Tumors
Antioxidants
Cancer Therapies and ROS
Therapeutic Role of Antioxidant Supplementation in Cancer
Pro-Tumorigenic Role of Antioxidants
Conclusion
References
185 Matrix Metalloproteinases (MMPs) in Cancer Immunotherapy
Introduction
MMPs and Tissue Inhibitors of Metalloproteinases (TIMPs) in Physiological Context
Functional Roles of MMPs in Cancer
Proteolysis of Extracellular Matrix
Modulation of Cellular Interaction, Migration, and Metastasis
Modulation of Growth Factors and Receptors
Tumor-Associated Angiogenesis
Regulation of Apoptosis
Immunomodulation and Inflammatory Response
Matrix Metalloproteinase Inhibitors (MMPIs) for Cancer Therapy
Peptidomimetic MMPIs
Non-peptidomimetic MMPIs
Tetracycline Derivatives
Off-Target MMPIs
Other Novel Mechanism-Based Selective MMPIs
Natural MMPIs
Monoclonal Antibodies as MMP Inhibitors
Matrix Metalloproteinase-Based Cancer Vaccines
Strategies to Enhance Immune Response to MMP-Based DNA Cancer Vaccines
Challenges and Future Prospect
References
186 Pathogens and Cancer
Introduction
Pathogenic Infections, Oxidative Stress, and Cancer
Helminth Parasites as Carcinogens
Schistosomiasis haematobium
Liver Flukes
Cestodes
Viruses as Carcinogens
Human Papilloma Virus
Hepatitis C Virus (HCV)
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Antioxidants as a Combinational Therapy for Cancer and Parasitic Infections
Conclusions
References
187 Susceptibility of Polymorphic GST as a Risk Factor in Oxidative Stress-Induced Cancer Development
Introduction
GST Genetic Variants
GST in Cancers
Role of GST in Lung Cancer
Role of GST in Breast Cancer
Role of GST in Liver Cancer
Role of GST in Colorectal Cancer
GST and Its Pharmacogenetics
Conclusion and Future Prospectus
References
188 Present Status of the Therapeutic Approaches to Treat Uveal Melanoma
Introduction
Genetic Contributors
Therapeutic Options
Chemotherapy
Targeted Therapy
Immunotherapy
Checkpoint Inhibition
Anti-CTLA-4 Therapy
Anti-PD-1 Therapy
Combined Inhibition of CTLA-4 and PD-1
Innovative Immune-Based Therapies
Epigenetic Control
Conclusions and Future Directions
References
189 Reactive Oxygen Species–Induced Cancer Cell Death: A Therapeutic Approach
Introduction
Cancer Treatment Modalities
Surgery
Radiation Therapy
Chemotherapy
Immunotherapy
Photodynamic Therapy
Types of Reactive Oxygen Species (ROS) and Photochemical Reactions
Sources of Reactive Oxygen Species
Mitochondria
Endoplasmic Reticulum
Peroxisomes
Exogenous Sources
Cellular Responses to ROS-Induced Oxidative Stress
ROS-Induced Apoptosis
ROS-Induced Autophagy
ROS-Induced Necrosis
Conclusion and Future Perspectives
References
190 Oxidative Stress in Cancer: Therapeutic Implications of Small-Molecule Kinase Inhibitors
Introduction
Small-Molecule Kinase Inhibitors (SMKIs)
Protein Kinase Inhibitors
Tyrosine Kinase Inhibitors (TKIs)
Serine/Threonine Kinase Inhibitors
PIM Kinase Inhibitors
Lipid Kinase Inhibitors
Dual PI3K/mTOR Inhibitors
Pan-PI3K Inhibitors
Isoform-Specific PI3K Inhibitors
Conclusion
Cross-References
References
191 Novel Developmental Therapeutics Targeting Human Oral Squamous Cell Carcinoma Through Reactive Oxygen Species-Mediated Apo...
Introduction
Endoplasmic Reticulum Stress
Has_circRNA_101036 as a Tumor Suppressor
Activation of ROS-Dependent ER Stress Through Disulfiram (Antabuse)
Alkylphosphocholine Erufosine as a Akt-mTOR Inhibitor
Extracellular Signal-Regulated Kinase (ERK)/MAPK Pathway
Isorhamnetin
Dihydroartemisinin
ROS-Regulated Mitochondrial Pathway
Surfactin from Bacillus subtilis
Lycorine Hydrochloride
Plant-Based Extracts
Azoxystrobin
Arglabin
Dietary Phytochemicals
Current Trends and Future Prospects
References
192 The Link Between Circadian Rhythm and ROS-Induced Cancer
Introduction
Circadian Rhythm
Physiological Basis of Circadian Rhythm and its Importance
Genetic Control of Circadian Rhythm
The Link between Circadian Clock and Cancer
ROS and Oxidative Stress
Oxidative Stress and Cancer
Cancer Cell vs Oxidative Stress and the Circadian Clock
Conclusion
References
193 Targeting the Antioxidant Enzymes for the Treatment of Reactive Oxygen Species (ROS)-Induced Cancer
Introduction
Antioxidant Enzymes
Alterations in the Antioxidant Enzymes During ROS-Induced Cancer
Alterations in Antioxidant Enzymes During Viral Induced ROS Production
Role of Antioxidant Enzymes in the Regulation of Epithelial-Mesenchymal Transition (EMT)
Antioxidant Enzymes as the Therapy/Therapeutic Target for Cancer
Statin-Based Therapy
SOD Mimics
GPx Mimics
CAT Mimics
DNA-Damaging Drugs
Conclusion
References
194 A General Overview on Causes, Risk Factors, Diagnosis, Treatment, and Role of Oxidative Stress Biomarkers in Colorectal Ca...
Introduction
Etiology
Molecular Pathophysiology of Colorectal Cancer
Molecular Signaling Pathways Involved in Colorectal Cancer
Wnt-β-Catenin Pathway
PI3K-AKT Pathway
RAS-RAF Pathway
NF-κB Pathway
GSK-3β (Acting as a Regulator in CRC Pathways)
Epithelial-to-Mesenchymal Transition (EMT)
Risk Factors
Diagnosis
Colonoscopy
Capsule Endoscopy
CT Colonography
Magnetic Resonance Imaging (MRI) and Endorectal Ultrasound (ERUS)
Biomarkers
Treatment Approaches
Surgery
Colon Surgery
Rectal Surgery
Quality Assurance and Recovery
Systemic Therapies for Primary CRC
Neoadjuvant Therapy
Adjuvant Therapy
Systemic Therapies for Metastatic CRC
Chemotherapy
Targeted Therapies
Role of Oxidative Stress Biomarkers in Colorectal Cancer
Future Perspectives
References
195 Oxidative Stress in the Pathogenesis of Ovarian Cancer
Introduction
Classification of OC
Epithelial Cell Carcinoma (ECC)
Germ Cell Cancer of the Ovary (GCC)
Stromal Cell Cancer of the Ovary (SCC)
Theories of Origin of OC (Saed et al. 2017)
Oxidative Stress on Ovarian Cancer
Common Ovarian Cancer Mutations Linked to ROS
Drug Resistant OC and Nrf2 Gene (Li et al. 2021)
Antioxidants and Therapeutic Targets in Ovarian Cancer (Amano et al. 2021)
Conclusion and Future Perspectives
References
196 Adipose-Derived Stem Cells
Introduction
ADSCs Characteristics
Relationship Between ADSCs and Cancer Cells
``Tumor Niche´´ ADSCs Relationship with Reactive Oxygen Species
ADSCs in Cancer Therapy
Conclusions and Perspectives
Cross-References
References
197 Translational Reprogramming of mRNA in Oxidative Stress and Cancer
Introduction
An Outline of mRNA Translation
mRNA Translation Initiation
Translation Elongation and Termination
Regulation of mRNA Translation Under Stress
Integrated Stress Response Involves Rewiring of mRNA Translation
mTOR Signaling Mediates Stress Adaptation by Controlling mRNA Translation
Translational Repression Induces Stress Granule Formation
tRNA Metabolism, Modification, and Cleavage Under Stress Impact mRNA Translation
Oxidative Stress and Translational Reprogramming
Oxidative Stress Induces Specific mRNA Translation Programs
tRNA Metabolism Is Altered in Oxidative Stress
Oxidative Stress Responsive Factors Modulate mRNA Translation
Controlling mRNA Translation: A Remedial Avenue in Cancer Therapeutics
Conclusions
References
198 Regulation of Cellular Stress in the Light of mRNA Alternative Polyadenylation
Introduction
Cellular Stress Response
Involvement of Cellular Processes in Stress
Signaling Pathways Regulating Stress-mediated Cell Death
Apoptosis
Autophagy
Necrosis
Regulation of Cellular Responses to Cope With Stress
ER Stress and Unfolded Protein Response
DNA Damage Responses and Cell Death
Oxidative Stress and Cell Death
mRNA 3′ End Processing and Its Mechanism
Cleavage/Polyadenylation Proteins
Mechanism of Alternative Polyadenylation
Regulation of Cellular Stress by Alternative Polyadenylation
Role of Cleavage/Polyadenylation Factors in Stress Response
Core Factors of APA
Auxiliary Factors of APA
The Role of Alternative Polyadenylation During DNA Damage Response
Role of Alternative Polyadenylation in Oxidative Stress
Role of Alternative Polyadenylation of Heat Shock Protein Encoding mRNAs
Role of Alternative Polyadenylation for Stress Related to Nutrient Deficiency
Role of Distal Polyadenylation Sites in Mammalian Cells in Response to Stress
Conclusion
Future Perspectives
References
199 Impact of Chemotherapeutic Drugs Towards Oxidative Stress and Associated Multi-organ Physiological Responses
Introduction
Cardiotoxicity
Chemotherapy-induced Cardiotoxicity Type I
Chemotherapy-induced Cardiotoxicity Type II
Hepatotoxicity
5-Flurouracil (5-FU)
Methotrexate
Irinotecan
Oxaliplatin
Tyrosine Kinase Inhibitors (TKIs)
Tamoxifen
Nephrotoxicity
Cisplatin
Ifosfamide
Vascular Endothelial Growth Factor (VEGF) Inhibitors (Bevacizumab)
Epidermal Growth Factor Receptor Inhibitors (Cetuximab)
Peripheral Neuropathy
Paclitaxel
Oxaliplatin
Thalidomide
Conclusion and Future Perspectives
References
200 The Role of Endothelin Axis and Reactive Oxygen Species in Future Therapies of Pancreatic Cancer
Endothelin
NADPH Oxidase and ROS
Endothelin and Pancreatic Cancer
Endothelin and Pancreatic Fibrosis
Endothelin and Pancreatic Stellate Cell Activation
Endothelin and Other Pancreatic Cells
Endothelin and Pancreatic Microcirculation
ROS and Pancreatic Cancer
ROS and Pancreatic Fibrosis
Hypoxia and Pancreatic Cancer
ROS and Pancreatic Cancer Signaling
DUOX1/2 and Pancreatic Cancer
Conclusions and Future Therapy
References
201 Targeting the Transcription Factors of ROS Tumorigenic Pathways as a Therapeutic Strategy in Cancer
Introduction
Transcription Factors in Cancer
DNA Damage Response and p53
P53 Signaling Networks
P53 Family Members
P73 and Tumor Suppression
P63 Signaling in Tumorigenesis
Targeting p53 Signaling for Cancer Therapy
Nuclear Factor-erythroid 2 p45-Related Factor-2 (NRF2)
NRF2: A Master Hub for Regulating Cellular Homeostasis
NRF2: A Pro-oncogene or Tumor Suppressor
NRF2 as a Target for Cancer Therapy
NRF2 Activation as a Therapeutic Strategy
NRF2 Inhibition as a Therapeutic Strategy
Hypoxia-Inducible Factors (HIFs)
Conclusion
References
202 Oxidative Stress in the Pathogenesis of Cervical Cancer
Introduction
Oxidative Stress and Cervical Cancer
Human Papillomavirus (HPV)
Genetic Alterations
Diagnosis
Treatment
Conclusion and Future Perspectives
References
203 Antioxidants in Oxidative Stress and Biocatalysts: Their Correlation with Cancer
Introduction
Oxidative Stress and Its Effect on the Body
Oxidative Stress Also Contributes to Aging
The Relationship Between Oxidative Stress and Cardiovascular Diseases
Clinical Significance
Enzymes and Antioxidants in Oxidative Stress
The Antioxidants Reported
Antioxidants in Medicinal Plants
Discussion
References
204 Biofluid Markers Unveiling Cancer Diagnosis and Prognosis: With Special Reference to Oxidative Stress
Introduction
Oxidative Stress as Biomarkers
Biomarkers in Various Human Biospecimens
Urinary Oxidative Stress Biomarkers
Oxidative Stress-Related Salivary Biomarkers
DNA Biomarkers
RNA Biomarkers: Salivary MicroRNA
Protein Biomarkers
Lysozyme
Alpha Amylase
Isoprostanes
Secretory IgA
Oxidative Stress Biomarkers in Blood
Blood MicroRNAs
Heat Shock Proteins
Enzymatic Antioxidants
Nonenzymatic Antioxidants
Cerebrospinal Fluid Biomarkers Related to Oxidative Stress
Oxidative Stress Levels in Pleural Effusion
Oxidative Stress Markers in Exhaled Breath Condensate
Expression of Oxidative Stress Biomarkers in Tears
Expression of Oxidative Stress Biomarkers in Sweat
Trace Elements Dyshomeostasis in Cancer Biofluids
Therapeutic Outcomes
References
Index