Preface
Contents
About the Editors
About the Section Editors
Contributors
1 Reactive Species and ER-Mitochondrial Performance for Glioblastoma Multiforme Treatment Strategy
Introduction
Current Status of Glioblastoma Multiforme (GBM)
Reactive Species and [Ca2+]i on ER Stress and Mitochondrial Performance
ER Stress, Mitochondria, and GBM
Genetic Alteration by Reactive Species in GBM
Angiogenesis, NADPH Oxidase, and GBM
Implications in the Treatment of Gliomas
Maintenance of Reactive Species Steady State
Targeting ER Components and Autophagy
Other Molecular Targets
Conclusion
References
2 Oxidative Stress and Thyroid Disorders
Introduction
Hyperthyroidism and OS
Papillary Thyroid Carcinoma and OS
Medullary Thyroid Carcinoma and OS
Anaplastic Thyroid Carcinoma and OS
Conclusion
References
3 Skin Cancer Induced by Pollution-Mediated ROS
Introduction
Solar Ultraviolet (UV) Radiation
Synergy: UVA Photo-Chemo Pollution
Ozone
Particulate Matter (PM)
Tobacco Smoke
The Aryl Hydrocarbon Receptor (AHR)
The Aryl Hydrocarbon Receptor (AHR) and Skin Cancer
Squamous Cell Carcinoma (SCC)
Basal Cell Carcinoma (BCC)
Malignant Melanoma
Topical Antioxidants to Protect from Environmental Pollution
Conclusion
Cross-References
References
4 Roles of β-Glucans in Oxidative Stress and Cancer
Introduction
Cancer
Carcinogenesis and Cachexia-Anorexia Syndrome
Risk Factors
Cancer Therapy
Oxidative Stress
Sources and Effects of Reactive Oxygen Species
ROS and Antioxidant Mechanisms
Cancer and Oxidative Stress
β-Glucans
Structural Characterization of β-D-Glucans
Anticancer Effects of β-Glucans
β-Glucans, Oxidative Stress, and Cancer
Conclusions
References
5 Oral Cancer and Oxidative Stress
Introduction
Oral Carcinogenesis
Oxidative Stress
Oxidative Stress and Oral Carcinogenesis
Conclusion
Cross-References
References
6 Oxidative Stress in Genitourinary Cancer
Introduction
Kidney Cancer
Urothelial Cancer
Prostate Cancer
Anticancer Therapy for Genitourinary Cancer and Oxidative Stress
Conclusions
References
7 Oxidative Stress, Microenvironment, and Oral Cancer
Introduction
Inflammation, Reactive Oxygen Species, and Cancer
Reactive Oxygen Species and Inflammation
Inflammation, Reactive Oxygen Species, and Cancer
Tumor Cell Survival
Tumor Cell Proliferation
Tumor Cell Invasion
Angiogenesis
Oral Squamous Cell Carcinoma and Reactive Oxygen Species
Tumor Microenvironment and Reactive Oxygen Species
Reactive Oxygen Species in Oral Cancer
Oncoviruses, Oral Squamous Cell Carcinoma, and Reactive Oxygen Species
Reactive Oxygen Species as an Appealing Target for Intervention (Table 8)
Reactive Oxygen Species as Alluring Targets for Therapeutic Intervention
Reactive Oxygen Species and Oral Potentially Malignant Disorders
References
8 Oxidative Stress and Glyoxalase Pathway in Cancer
Introduction
Glyoxalase System
Glyoxalase I (GLOI)
Glyoxalase II (GLOII)
Glyoxalase III (GLOIII)
Methyglyoxal and Cancer
Methylglyoxal-Induced Reactive Oxygen Species (ROS)
Glyoxalase Enzymes and Cancer
Tumor Hypoxia, Cancer Cell Stemness, and Glyoxalase Expression
Dual Role of Glyoxalase I in Cancer
Modulation of Cellular Pathways by GLOI Overexpression
Effect of Ionizing Radiation on Glyoxalase Expression
Therapeutic Potential of Glyoxalase Pathway in Cancer
Exogenous Application of Methylgloxal for Cancer Therapy
Inhibition of Glyoxalase Enzymes as Treatment Modality in Cancer
Phytochemicals as Modulators of Glyoxalase Pathway
Naringin
Galangin
Curcumin
Oleuropein (OP)
Conclusions and Future Directions
References
9 The Implication of ROS Homeostasis in the Modulation of EMT Signaling and Its Role in Manipulating Tumor Microenvironment
Introduction
The Implication of Reactive Oxygen Species in Favoring Epithelial-to-Mesenchymal Transition (EMT)
ROS as a Signaling Molecule Controlling Pro-metastatic Responses
Regulation of Cytoskeletal Proteins by Reactive Oxygen Species: Consequences on Cellular Motility
Manipulations of Tumor Microenvironment by Reactive Oxygen Species to Expedite Metastasis
The Integrative Role of ROS During Hypoxia in Facilitating Tumor Metastasis and Angiogenesis
Conclusion
References
10 Functional Regulation Between Matrix Metalloproteases and Cell Junction Proteins in Gastric Cancer
Introduction
Matrix Metalloproteinases (MMPs) and Gastric Cancer
Cell Junction Proteins in Gastric Cancer
Tight Junctions
Gap Junction
Adherens Junction
Crosstalk Between of MMPs and Cell Junction Proteins
MMP and Adherence Junction Proteins
MMPs and Tight Junction Proteins
MMPs and Gap Junction Proteins
Conclusion and Future Directions
References
11 Association of Oxidative Stress and Mitochondrial Dysfunction to Gynecological Malignancies
Introduction
Oxidative Stress, ROS, and Antioxidants
ROS Paradox: Dual Effect on Cancer Cells
Mitochondria as a Hub of Intrinsic ROS Generation
mtROS: Prime Oncogenic Factor
ROS: A Key Driver of Gynecological Cancer Progression
ROS-Driven Metabolic Reprogramming: A Prime Hallmark of Cancer
Implications of ROS-Induction on Signaling Aberrations in Cancer
ROS Synchronizes Tumor Microenvironment Components in Gynecological Cancers
ROS-Based Therapeutic Implications in Cancer
Conclusion
References
12 Impact of Caenorhabditis elegans in Cancer Drug Resistance Development
Introduction
Hormesis
Cancer and Chemoresistance
Hormetic Stressors
Conclusion
References
13 Scaffold-Based Selective ROS Generation as Viable Therapeutic Strategies Against Cancer
Introduction
Background
Molecular Basis of ROS Production
ROS Paradox in Cancer
Modulation of ROS as a Therapeutic Target
Reduction of ROS Levels: Antioxidants and Nutraceuticals
Induction of ROS Levels: Scaffold-Based Chemotherapeutics
Quinone
Nitrogen Mustard
Nitrosoureas
Organic Endoperoxides
Organic Di- and Polysulfides: Diallyl Trisulfide and Varacin
Organosulfur Isothiocyanate: Sulforaphane and β-Phenylethylisothiocyanate
Peptide and Nucleoside
Taxane, Alkaloid, and Steroid
Non-metal and Metal
Miscellaneous Scaffolds (Procarbazine, Elesclomol, Erastin, Celecoxib)
Prodrug (Masking-Demasking)
Conclusion and Future Direction
Cross-References
References
14 Targeting Oxidative Stress in Cancer
Introduction
Mechanism of Oxidative Stress Toward Carcinogenesis
Amelioration of Oxidative Stress Toward Prevention of Cancer
Natural Compounds
Some Natural Compounds Act as Antioxidants (Table 1)
Role of Synthetic Compounds
Biomimic or Nanoflowers
Advanced Therapeutics
Targeted Therapy
Conclusion
References
15 Targeting Mitochondria as a Novel Disease-Modifying Therapeutic Strategy in Cancer
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
16 Cutaneous Unfolded Protein Response (UPR) and Endoplasmic Reticulum (ER) Stress
Introduction
Sensor-Transducers of the Cutaneous UPR: A Mechanistic Overview
The Cutaneous UPR and Environmental Stressors: An Overview
The UPR and Skin Photodamage
The Cutaneous UPR and Ionizing Radiations
The Cutaneous UPR and Toxic Metals
The Cutaneous UPR and Paraquat
The Cutaneous UPR and Cigarette Smoking
The UPR and Particulate Matter
The UPR and Chlorine Exposure
The UPR and Phenolics
The Cutaneous UPR and Cosmetic Products
The UPR and the Lewisite
The Cutaneous UPR and Sulfur Mustard
The Cutaneous UPR and Formaldehyde Exposure
Viruses and Cutaneous UPR
Bacteria and Cutaneous UPR
The UPR Link with Cutaneous Pathologies
Role of UPR in Skin Keratinization and Darier´s Disease
Role of UPR in Keratosis Linearis with Ichthyosis Cogenita and Keratoderma (KLICK) Syndrome
Role of UPR in Erythrokeratoderma Variabilis (EKV)
Role of UPR in Ichthyosis Follicularis with Atrichia and Photophobia (IFAP) Syndrome
Role of UPR in Keratosis Follicularisspinulosa Decalvans (KFSD)
Role of UPR in Rosacea
Role of UPR in Epidermolysis Bullosa Simplex
Targeting ER Stress for Therapy
Therapeutic Targeting of Abnormal UPR in Hereditary Keratosis
Enhancing Protein Folding Capacity
Targeting Individual UPR Pathways
IRE1α Inhibitors
PERK Inhibitors
ERAD Modulators
Modulators of ER Chaperones of ER Stress Signaling
Concluding Remarks and Future Directions
References
17 Iron Sulfur Clusters and ROS in Cancer
Introduction
Iron Sulfur Clusters Proteins: Types of Fe-S
Biochemistry of Fe-S Proteins
Major Proteins Containing Iron Sulfur Clusters in Biological Systems
Fe-S Cluster Biosynthetic Machinery
Mitochondrial Iron-Sulfur Cluster (ISC) Assembly Machinery: Proteins and Steps
Oxidative Stress and Fe-S Cluster Damage
How Iron-Sulfur Clusters Generate Reactive Oxygen Species
Iron Sulfur Cluster Proteins Linked with Cancer
MitoNEET- the Redox Sensor
Iron-Sulfur Cluster Assembly Enzyme
Aconitase -the Fe-S Regulator
Frataxin
Nutrient-Deprivation Autophagy Factor-1 (NAF-1)
Ferredoxin Reductase
Therapeutic Drugs for Cancer That Use or Target Fe-S Clusters
Drugs That Generate ROS Via Fe-S Clusters
Conclusion
References
18 Free Radicals, Reactive Oxygen Species, and Their Biomarkers
Introduction
Free Radicals and Reactive Oxygen Species
Radicals and Free Radicals
Reactive Oxygen Species and Oxygen Free Radicals
Metal Free Radicals
Iron
Copper
Manganese
Zinc
Oxidative Stress Biomarkers in Cancer
Single Oxidation or Antioxidant
Total Oxidant Status, Total Antioxidant Status, and Oxidant Stress Index
Measurement of Total Antioxidant Status
Measurement of Total Oxidant Status
Calculation of Oxidant Stress Index
End Products of Lipid Hydroperoxide
Conclusions
References
19 Zymographic Techniques
Introduction
Matrix Metalloproteinases in Cancer
Types of Zymographic Techniques
Basic Protocol of Zymography to Map MMP Activities
Materials for Zymography Experiment
Sample Preparation
Preparation of Gel
Sample Loading and Gel Electrophoresis
Analysis
Antioxidative Enzymes as Cancer Target
Zymographic Techniques for Antioxidative Enzymes
Zymography Protocol for Catalase Enzyme
Zymography Method for SOD Enzyme
Conclusion
References
20 Biomarkers of Oxidative Stress and Its Dynamics in Cancer
Introduction
Mitochondrial Biomarkers of Oxidative Stress
Regulation of Mitochondrial Dynamics and Its Biogenesis
Oxidative Stress in Mitochondrial Dynamics and Its Pathophysiology
Pharmacological Strategies to Target Oxidative Stress Biomarkers
Impact of Oxidative Stress in Mitochondrial Dynamics
Conclusions
References
21 Glutathione as Oxidative Stress Marker in Cancer
Introduction
Reduced and Oxidized Glutathione
Prodrugs and Co-drugs of GSH
Cancer and Oxidative Stress Mechanism
Phase 1 and Phase 2 Detoxification Pathways
Phase 1 Pathway
Phase 2 Pathway
Metal Homeostasis
Chromium
Copper
Iron
Glutathione, Metallothionein, and Cancer
Glutathione, Free Radicals, and Antioxidants
Free Radicals and Reactive Oxygen
Antioxidants
ROS and Antioxidants Balance
Cancer and Glutathione
Glutathione, Cancer, and Oxidative Stress
Type of Mechanism on Glutathione as a Marker for Cancer
Other Oxidative Stress Markers Resembling Glutathione (Benedette 2018; Payal et al. 2016) (Table 3)
The Role of Selenoproteins and Glutathione in Cancer
Antioxidants May Make Cancer Worse
Conclusion
Cross-References
References
22 Salivary Oxidative Stress Biomarkers in Oral Potentially Malignant Disorders and Squamous Cell Carcinoma
Introduction
Salivary Diagnostics
Tumor Biomarkers and Its Significance
Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders
Oxidative Stress Biomarkers
Salivary Oxidative Stress Biomarkers in Oral Cancer
Conclusion
Cross-References
References
23 Recent Development of Monoclonal Antibodies Targeting Tyrosine Kinase in ROS-Mediated Cancer
Introduction
Reactive Oxygen Species (ROS) and Its Importance in Cancer and Its Treatment
MAbs-Based Therapy for ROS-Mediated Cancer
Recent Development of mAbs Targeting Tyrosine Kinase of ROS-Mediated Cancer
Anti-EGFR Monoclonal Antibodies
Anti-HER2 Monoclonal Antibodies
Future Scope and Conclusion
References
24 Fluoride as a Carcinogen: A Myth or Fact?
Introduction
Fluoride and Cancer
Fluoride and Apoptosis
Conclusions
References
25 The Role of ROS in Chemical Carcinogenesis Induced by Lead, Nickel, and Chromium
Introduction
The Role of ROS in Chemical Carcinogenesis Induced by Lead
The Role of ROS in Chemical Carcinogenesis Induced by Nickel
The Role of ROS in Chemical Carcinogenesis Induced by Chromium
Concluding Remarks
References
26 Environmental Contaminants, Oxidative Stress, and Reproductive Cancer
Introduction
Epidemiological Aspect of Reproductive Cancer
Environmental Causes of Female Reproductive Cancer
Environmental Causes of Male Reproductive Cancer
Endocrine Disruptors and Reproductive Cancer
Pesticides and Reproductive Cancer
Obesogens and Reproductive Cancer
Oxidative Stress and Reproductive Cancer
Antioxidants and Reproductive Cancer
Conclusions
References
27 Environmental Toxicants and Carcinogenicity: Role of Oxidative Stress
Introduction
Heavy Metals, Oxidative Stress, and Cancer
Pesticides, Oxidative Stress, and Cancer
Conclusion
References
28 Environmental and Occupational Exposure to Pesticides and Cancer Development
Introduction
Environmental and Occupational Exposure to Pesticides
Herbicides
Organochlorine Pesticides
Organophosphate Pesticides
Conclusion
References
29 Benzo(a)Pyrene-Induced ROS-Mediated Lung Cancer
Introduction
Benzo(a)Pyrene and Lung Cancer
Source and Route of B(a)P
B(a)P Metabolism
B(a)P and Oxidative Stress
Radical Cations and B(a)P
Redox-Active Quinone Radical
DNA Adducts
Oxygen Free Radicals and DNA Adducts
Role of Free Radicals in Cigarette Smoking
Role of Oxygen Radicals in Initiating Tumors
Oxygen Radicals as Tumor Promoters
Conclusion
References
30 Essential Role of Occupational Hazards in Cancer Among Women
Introduction
Breast Cancer
Colon Cancer
Gastrointestinal Cancers
Ovarian and Uterine Cancers
Lung Cancer
Skin Cancer
Conclusion
References
31 Arsenic: An Environmental Toxicant-Induced Oxidative Stress and Carcinogenesis
Introduction
Skin Cancer
Lung Cancer
Bladder Cancer
Liver Cancer
Kidney Cancer
Cellular Metabolism of Arsenic
Role of ROS in Arsenic Carcinogenicity
Conclusion
Cross-References
References
32 ROS in Apoptosis of Cancer Cells
Introduction
Definitions for Cancer Cells, ROS, and Apoptosis
Relationship Between Apoptosis and ROS
ROS in Regulation of the Mitochondrial or Intrinsic Apoptotic Pathway
ROS in Regulation of the Death Receptor or Extrinsic Apoptotic Pathway
Apoptosis of Cancer Cells Triggered by ROS
Conclusion
References
33 Role of ROS in Triggering Death Receptor-Mediated Apoptosis
Introduction to Apoptosis
Apoptosis Signaling Pathways
General Features of Apoptosis
Caspase
Main Mechanisms of Apoptosis Regulation and Execution
The Mitochondrial or Intrinsic Pathway
The Death Receptor or Extrinsic Pathway
Endoplasmic Reticulum Pathway
ROS and Apoptosis
The Intrinsic Pathway and ROS
ROS and the Extrinsic Pathway
The ER Pathway and ROS
ROS in Apoptosis and Cell Survival in Cancer Cells
ROS Mediator and Executor of Apoptosis
Conclusions
References
34 Advanced Glycation End Products-Mediated Oxidative Stress and Regulated Cell Death Signaling in Cancer
Introduction
Receptor for Advanced Glycation End Products (RAGE)
AGES and RAGE in Cancer
Oxidative Stress and AGE/RAGE Signaling in Cancer
AGE/RAGE and Regulated Cell Death Signaling in Cancer
Conclusion
References
35 Helping Leukemia Cells to Die with Natural or Chemical Compounds Through H2O2 Signaling
Introduction
An Enemy Within Myself
Making Fun of Death
Oxidative Distress: The Dose Makes Life or Death Signals
H2O2: ``A match that starts bush fires´´
Quo Vadis?
Conclusion
References
36 Microtubule-Targeting Agents Induce ROS-Mediated Apoptosis in Cancer
Introduction
Importance of Microtubules in Anticancer Therapy
ROS: A Friend or Foe
ROS in Cancer Development and Metastasis
Cytotoxic Role of ROS in Cancer Cells
Mitochondria: The Missing Link Between MTAs and ROS Generation in Cancer Cells
Modulation of ROS-Mediated Apoptotic Signaling by MTAs
Microtubule Targeting Agent Kills Cancer Cells by Modulating ROS Induced Autophagy
Conclusion
References
37 ROS Induced by Chemo- and Targeted Therapy Promote Apoptosis in Cancer Cells
Introduction
ROS: A Double-Edged Sword
ROS as an Oncogene
ROS as a Tumor Suppressor
ROS-Mediated Apoptosis in Malignant Cells by Targeted Therapy
Tyrosine Kinase Inhibitors
PIM Kinase Inhibitors
ROS-Mediated Apoptosis in Malignant Cells by Chemotherapy
Strategies and Drugs Targeted to Increases ROS-Mediated Apoptosis in Malignant Cells
Conclusion
Cross-References
References
38 ROS-Mediated Apoptosis in Cancer
Introduction
ROS in the Mitochondria-Mediated Intrinsic Apoptotic Pathway
ROS in the Death Receptor-Mediated Apoptotic Pathway
ROS in p53-Mediated Apoptosis
ROS in ER Stress-Induced Apoptosis
ROS in Calcium-Mediated Apoptosis
Prooxidant-Based Cancer Therapy
Conclusion
Cross-References
References
39 Genomic Instability in Carcinogenesis
Introduction
Genomic Instability - An Overview
Genomic Instability and Cancer
The Role of Oxidative Stress in Genomic Instability in Cancer
Oxidative Stress Induced Genomic Instability in Carcinogenesis: Mechanism and Evidences
The Role of Oxidative Stress-Induced Lipid Peroxidation in Genomic Instability
Cellular Defense Mechanism against Oxidative Stress-Induced Genomic Instability
Conclusion and Future Perspectives
References
40 Impact of Environmental and Occupational Exposures in Reactive Oxygen Species-Induced Pancreatic Cancer
Introduction
Epidemiology of Pancreatic Cancer with Incidence and Prevalence
Prevalence/Geographic Distribution of Pancreatic Cancer
Environmental, Occupational, Lifestyle, and Genetic Risk Factors for Pancreatic Cancer
Age, Gender, and Race
Smoking and Tobacco
Alcohol
Dietary Factors
Vitamin D and UVB Irradiation
Obesity
Occupational Exposures of Heavy Metals
Chronic Pancreatitis
Infections
Genetic Risk Factors
Current Treatment of Pancreatic Cancer
Reactive Oxygen Species (ROS)/Oxidative Stress Promotes Cancer Development
Reactive Oxygen Species (ROS) in Relation to Pancreatic Adenocarcinoma
Environmental Risk Factor of Pancreatic Cancer: Tobacco Smoking in Relation to Reactive Oxygen Species
Occupational Risk Factor of Pancreatic Cancer: Cadmium Heavy Metal in Pesticide in Relation to Reactive Oxygen Species (ROS)
Cadmium
Conclusions
References
41 Reactive Oxygen Species: Central Regulators of the Tumor Microenvironment
Introduction
The Origin of ROS: Mitochondrial and Nonmitochondrial Sources
Major Producers of ROS in the TME
Molecular Events Triggered by ROS: Impact on Tumorigenesis
Modulation of Immune Cells by Tumor Microenvironment-Associated Oxidative Stress
Natural Killer Cells
Dendritic Cells
T-Cells
Treg Cells
ROS Involvement on Immunomodulation by Antitumor Therapeutics Immunotherapy
Conclusion
References
42 Biomarkers of Oxidative Stress-Induced Cancer
Introduction
Oxidative Stress and Cancer
Biomarkers of Oxidative Stress and Role in Cancer Diagnosis and Treatment
Oxidative Stress Biomarker Research in Breast Cancer
Oxidative Stress Biomarker Research in Gastro-Intestinal and Colorectal Cancer
Oxidative Stress Biomarker Research in Prostate Cancer
Biomarkers of Oxidative Stress Research in Lung Cancer
Biomarkers of Oxidative Stress Research in Ovarian Cancer
Biomarker of Oxidative Stress in Cervical Cancer
Conclusion
References
43 Reactive Oxygen Species in Male Reproductive Cancers
Introduction
ROS in Prostate Cancer Development
Imbalance in ROS Generation and Antioxidant Protection in Prostate Leads to mtDNA Mutations
Mutations in Mitochondrial Genome and Correlation with Prostate Cancer
NADPH Oxidase Is a Source of ROS for Prostatic Cancer Cells
Androgens in Regulation of ROS Generation in Prostate Cancer
Ageing and ROS in Incidence of Prostate Cancer
Cancer Prevention by Dietary Antioxidants?
Testicular Cancer
Regulation of ROS and Aerobic Glycolysis in Testicular Cancer
Heat Stress and Testicular Cancers
Penile Cancer
SOD2 as a Marker for Penile Cancer Metastasis
Targeting ROS for Cancer Therapy
Conclusions and Future Directions
Cross-References
References
44 Biomarkers of Oxidative Stress in Cancer and Their Clinical Implications
Introduction
Reactive Oxygen Species and Oxidative Stress
Cellular Sources of ROS
Cellular Signaling Mediated by ROS
The Antioxidant System
ROS Influences Signaling Pathways in Cancer
Inflammation and Oxidative Stress in Cancer
Biomarkers of Oxidative Stress
End Products of Lipid Oxidation
By-products of DNA Oxidation
By-products of Protein Oxidation
Other Biomarkers of Oxidative Stress in Cancer
ROS Markers: Methods of Measurement
Direct Measurement of ROS
Superoxide
Hydrogen Peroxide
Nitric Oxide
Peroxy-Nitrite
Assessing the Damage to Macromolecules Such as DNA, Proteins, and Lipids
Protein Damage
Lipid Damage
DNA Damage
Measurement of Antioxidant Levels
Enzymatic Antioxidants
Superoxide Dismutase
Catalase
Glutathione Peroxidase
Nonenzymatic Antioxidants
Glutathione
Vitamin-C
Vitamin-E
Clinical Implications of Oxidative Stress Markers in Cancer
ROS-Induced Apoptosis
ROS-Induced Autophagy and Necrosis
ROS-Induced Necrosis
ROS-Mediated Resistance to Cancer Therapy
ROS as a Marker of Risk Prediction and Prognosis in Cancer
Conclusion
References
45 The Role of Reactive Oxygen Species on Cellular Fate and Function of Tumor-Infiltrating Lymphocytes
Introduction
Role of ROS as Signaling Molecules in Cancer
ROS and the Immune System
ROS and Innate Immunity
ROS in Adaptive Immunity
ROS Production in the Tumor Microenvironment
MDSCs
Tumor-Associated Macrophages
Tumor Cells
ROS and Tumor-Infiltrating Lymphocytes
Mechanisms of Action of ROS on Tumor-Infiltrating T Lymphocytes
T Cell Hyporesponsiveness
Altered T Cell Activation
T Cell Death
Therapeutic Strategies that Affect ROS and Influence Anti-tumor Immunity
Conclusions
References
46 ROS-Mediated Inflammatory Response in Cancer
Introduction
Production of ROS
ROS from Mitochondria
ROS from Oxidase Activity
ROS from Peroxisomes
Chronic Inflammation and Cancer
Oxidative-Stress-Induced Inflammation
Molecular Mechanisms of ROS-Induced Carcinogenesis
DNA Damage
Role of ROS in DNA Damage Induced by Replication Stress/Other Factors
Cell Signaling Cascades in ROS-Mediated Inflammation and Cancer
Transcription Factors - NF-κB, STAT, AP-1, HIF-1
Apoptosis and Survival
Inflammatory Markers and ROS
Tumor Microenvironment
Components and Characteristics of TME
Hypoxia, Angiogenesis, and Metastasis
ROS in Cancer Metastasis
Angiogenesis and ROS
Regulation of ROS
Conclusion
References
47 Food Colors and Associated Oxidative Stress in Chemical Carcinogenesis
Introduction
Use of Synthetic Dyes
International Legislations
Regulation in the European Union
Regulation in the USA, Japan, and China
Regulatory Measures in India
Carcinogenicity of Food Dyes
Oxidative Stress
Genotoxicity
Neurotoxicity
Biotransformation
Oxidative Effects and Associated Health Risks of Synthetic Dyes
Health Concerns of Approved Dyes
Health Concerns of Illegal Dyes
Conclusions
Cross-References
References
48 Benzo(a)Pyrene-Induced Oxidative Stress During Lung Cancer and Treatment with Baicalein
Introduction
Lung Cancer
Epidemiology and Incidence Statistics
Known Risk Factors
Polycyclic Aromatic Hydrocarbons (PAHs)
Benzo(a)pyrene [B(a)P]
B(a)P: A Potent Inducer of Oxidative Stress
B(a)P-Induced Inflammatory Responses
Mechanisms of B(a)P-Induced Lung Cancer
Lung Cancer Progression Stages
Traditional Treatment for Oxidative Damage and Lung Cancer
Free Radical Scavenging and Antioxidant Activity of Baicalein
Anti-Inflammatory Activity of Baicalein
Conclusion
References
49 Assessing the Contributions of Lipid Profile and Oxidative Lipid Damage to Carcinogenesis
Introduction
Lipids: Key Macromolecules with Structural and Functional Diversities
Body
Carcinogenesis Through Inflammation
Redox Homeostasis: Oxidative Stress and Antioxidant Defense
ROS and Lipid Peroxidation in Physiological and Pathophysiological Conditions
Dietary, Blood, and Biomembrane Lipid Composition and LPO Products
Mechanism of Carcinogenesis Through LPO and Inflammation
Organelle Dysfunction Caused by LPO Products
Lipid Peroxidation and Its Products: Structure, Signalling, and Cellular Biochemical Effects
Conclusion
References
50 Oxidative Stress in Hepatocarcinogenesis and Role of Antioxidant Therapy
Introduction
Liver Cells and Inflammatory Cytokines
Mitochondrial Roles in ROS-Induced Hepatocarcinogenesis
Viral Hepatitis Increases Free Radicals: Toward HCC Induction
Alcohol and Oxidants Cause HCC
Warburg Effect Increases Oxidative Stress in HCC Cells
Current Preventive and Treatment Modalities of HCC and Related Limitations
Antioxidant Therapy for HCC
Natural Honey
Nigella sativa
Ajwa Date Fruit
Costus
Fennel (Foeniculum vulgare Mill)
Conclusion
References
51 Oxidative Stress in Orchestrating Genomic Instability-Associated Cancer Progression
Introduction
Oxidative Stress: Its Generation and Implication in Cancer
Oxidative Stress-Mediated DNA Damage Leads to Genomic Instability
Chromosomal Instability
Telomere Shortening
Centrosome Amplification, Multipolarity, and Centrosome Clustering
Microsatellite Instability
Epigenetic Modifications
Oncogenic Replication Stress
Oxidative Stress Manipulates DNA Damage Response to Facilitate Genomic Instability
Therapeutic Strategies to Mitigate Genomic Instability in Cancer Progression
Amelioration of Oxidative Stress to Prohibit Establishment of Genomic Instability
Increasing Oxidative Stress to Kill Cancer Cells Via Comprehensive Genomic Degradation
Conclusion
References
52 Hypoxic Stress Perturb DNA Repair Mechanisms Leading to Genetic Instability
Introduction: The Hypoxic Tumor Microenvironment
Hypoxia and Reoxygenation Induces Oxidative Stress Through Reactive Oxygen Species (ROS)
Hypoxia and the Activation of DNA Damage Response
Downregulation of DNA Repair Pathways Under Hypoxia
Base Excision Repair (BER)
Nucleotide Excision Repair (NER)
Mismatch Repair (MMR) Pathway
Homology-Directed Repair (HDR)
Non-Homologous End Joining (NHEJ)
Fanconi Anemia (FA) Pathway
Hypoxia Induced Replication Stress
Hypoxia Induced Genetic Instability
Conclusion
References
53 DNA Lesions Induced by Lipid Peroxidation Products in Cancer Progression
Introduction
DNA Lesions Induced by Reactive Lipid Peroxidation Products
Malondialdehyde
α,β-Unsaturated Aldehydes
Propano Adducts
Etheno Adducts
Ketoaldehydes
DNA Lesions from Lipid Peroxidation in Cancer Development
Conclusion
Cross-References
References
54 Understanding ROS-Induced DNA Damage for Therapeutics
Introduction
Relevance of ROS-Induced Oxidation in Pathogenesis of Cancer
ROS Interaction with Lipids
Generation Cytosolic ROS from Proteins
Ras Signaling
PI3-K/Akt Pathway
IKK/NF-κB Pathway Regulation by ROS
ROS and Nuclear Signaling
Oxidative Stress Promotes Cancer
ROS Serves Dual Purpose in Cancer
Cancer Progression and Metastasis Are Promoted by CAFs
ROS and Cellular Death Pathways
Apoptosis
Caspases
Autophagy and ROS (Programmed Cell Death Type II)
Necrosis and ROS
Necroptosis (Programmed Cell Death: Type III)
Ferroptosis and ROS
Therapeutics and ROS
ROS and Multidrug Resistance
Nuclear ROS Induces DNA Damage
ROS Targeted Nanotherapeutic Drugs
Conclusion
References
55 Mitochondrial Metabolism, Oxidative Stress, and the Microenvironment in Breast Cancer Development and Progression
Introduction
The Role of Mitochondrial Metabolism in Breast Cancer Development and Progression with Focus on Mitochondria and ROS Production
The Importance of Mitochondria for Cancer Cell Metabolism
Mitochondrial Functions in Non-cancer Cells and Changes in Cancer Cells
The Breast Tumor Microenvironment, Metabolic Interactions and Crosstalk Between Stroma and Tumor Cells
Oxidative Stress as an Essential Factor in the Pathogenesis and Progression of Breast Cancer
ROS and Oxidative Stress
Triggers for ROS Production and Oxidative Stress
Oxidative Stress Affecting Sites Distal from Tumor Tissue
Conclusions and Perspectives
References
56 Role of Oxidative Stress and DNA Damage/Repair in Lung Cancer
Introduction
Inducers of Lung Cancer
Genetic Factors
Epigenetics and Lung Cancer
Environmental Factors
Link Between Inflammation, Oxidative Stress, and DNA Damage
Vicious Cycle Between Inflammation and DNA Damage in Development of Lung Cancer (Fig. 1)
Relation Between Various Chronic Inflammatory Lung Diseases and Lung Cancer
Sources of Reactive Oxidative Species (ROS) in Lung Cancer
DNA Repair Mechanisms in Lung Cancer
Oxidative Stress/DNA Damage Markers in Lung Cancer
Therapeutic Targets in Lung Cancer in Oxidative Stress, DNA Damage, and DNA Repair
Controversial Role of Oxidative Stress in Lung Cancer
Important Clinical Trials Targeting Redox Candidates in Lung Cancer
Conclusions and Future Direction
References
57 Oxidative Stress and Cancer: Role of the Nrf2-Antioxidant Response Element Signaling Pathway
Introduction
Oxidative Stress and Cancer
Oxidative Stress
Oxidative Stress and Carcinogenesis
The Nrf2-Antioxidant Response Element (Nrf2-ARE) Signaling Pathway
The Double Role of Nrf2 in Cancer
Pro-Oncogenic Effects of Nrf2: Nrf2 as a Proto-Oncogene
Nrf2 as Tumor Suppressor
Mechanisms of Nrf2 Activation in Cancer Cells
Somatic Mutations of Keap1, Nrf2, and Cul3
Epigenetic Modifications of Keap1
Disruption of Nrf2/Keap1 Interactions by Other Signaling Pathways
Role of Nrf2 in Chemoresistance
Conclusions
Cross-References
References
58 Role of Macrophages in Oxidative Stress-Induced Inflammatory Tumor Microenvironment
Introduction
Oxidative Stress and Chronic Inflammation: Important Regulators of Tumor Progression
Source of Oxidative Stress Within the Tumor Microenvironment
Cancer Cells
Microenvironmental Factors
Stromal Cells
Relationship Between Oxidative Stress, Tumor, and Chronic Inflammation
Cancer Cells and the Inflammatory Response
Maintenance of Chronic Smoldering Inflammation in the Tumor Microenvironment
Oxidative Stress in Tumors Prevents Suppression of Inflammation, Leading to Chronic Inflammatory Conditions
Recruitment and Oxidative Stress Mediated Differentiation of Leucocytes into Pro-tumorigenic Type
Recruitment of Monocytes to the Tumor Microenvironment
TME Mediated Activation of Recruited Monocytes
Both Tumor and TAM Derived ROS Influence Macrophages Function
Macrophage Differentiation and Oxidative Stress
Conclusion
References
59 The Triad, Hypoxia-ROS-Inflammation
Introduction
Oxidative Stress, Inflammation, and Hypoxia: Vicious Cycle
Effects of Oxidative Stress, Hypoxia, and Inflammation on Host Immune System
Tumor-Oxidative Stress, Hypoxia, and Inflammatory Mediators Directly Affect T Cell Survival and Function
Tumor Microenvironment and Oxidative Stress Cause Phenotypic Alteration of Macrophages and Immature Myeloid Lineage Cells
Regulatory T Cells and Tumor Microenvironment Factors
Targeted Immunotherapy of Cancer and Oxidative-Inflammatory Barrier
Conclusion
Cross-References
References
60 Interplay Between Reactive Oxygen Species and Key Players in the DNA Damage Response Signaling Network
Introduction
Components of the DDR Signaling System
The MRN Complex
ATM/ATR
H2AX
53BP1
DDR and Redox-Sensitive Transcription Factors
p53
NF-κB
NFE2L2
ROS at the Crossroads of Cell Proliferation and Apoptosis
Therapeutic Implications of DDR-ROS Interplay
Conclusions
References
61 ROS at the Intersection of Inflammation and Immunity in Cancer
Introduction
Oxidative Stress: Generation and Impact
An Essential Pillar of Innate Immunity: Nod-Like Receptors
ROS, Inflammation, and Immunity
The Interplay Between Oxidative Stress, Inflammation, and Immunity in Cancer
Therapeutic Implications
Conclusions
References
62 Sestrin-2 Connects Autophagy: Gatekeepers Against Tumor Progression
Introduction
Sestrin Family of Genes
Oxidative Stress and Sestrins
Cellular Effects of Sestrins
Sestrins: Gatekeepers Against Cancer
p53-Sestrin-AMPK Connection
Sestrin Regulation of Nrf2/Keap1 and ER Stress Pathways
Mechanism of Autophagy
Sestrin Connects Autophagy in Cancer
Sestrin 2 and Mitophagy
Conclusion
References
63 Insights into the Role of NRf2 Pathway in Cadmium-Induced Carcinogenesis
Introduction
Mechanism of Cadmium-Mediated Carcinogenesis
Role of ROS in Cadmium-Induced Cancer
Modulation of Nrf2-Mediated Pathway in Cadmium-Induced Cancer
Conclusion and Future Prospects
References
64 Interplay Between Redox Homeostasis and Oxidative Stress in the Perspective of Ovarian and Cervical Cancer Immunopathogenes...
Introduction
Nexus Between ROS, Cancer, and Immune Cells
Chronic Inflammation-Related Oxidative Stress in the Pathogenesis of Ovarian and Cervical Cancers
Oxidative Stress in Ovarian and Cervical Cancer Initiation
Oxidative Stress in Ovarian and Cervical Cancer Promotion
Oxidative Stress in Cell Proliferation and Survival
Oxidative Stress in Angiogenesis
Oxidative Stress in Immune Suppression
Oxidative Stress in Ovarian and Cervical Cancer Progression
Modulation of ROS as Cancer Therapy
Chemotherapy
Doxorubicin
Platinum-Based Drugs (Cisplatin, Carboplatin)
Paclitaxel
Poly (ADP-Ribose) Polymerase (PARP) Inhibitors
Immunotherapy
Conclusion
Cross-References
References
65 Oxidative Dyshomeostasis in the Mitochondria
Introduction
Oxidative Stress and Cancer
Mitochondrial Alterations in Cancer
Origins of Oxidative Stress
What Happens to Mitochondrial Antioxidants in Cancer Cells?
Metabolic Modulations in the Tumor Microenvironment
mtDNA Mutations in Cancer
Cancer Cells Manipulate Mitochondrial Functions to Resist Apoptosis and Favor Autophagy
Mitochondrial Oxidative Stress in Tumor Growth and Metastasis
Applications of Mitochondrial Variability in Diagnosis and Staging of Cancer
mtDNA Markers of Tumors
Mitochondrial Metabolic Markers for Tumors
Mitochondrial Oxidative Stress-Associated Cancer Therapy Approaches
Conclusion
References
66 The Double-Edged Sword Role of ROS in Cancer
Introduction
Role of ROS in Tumor Promotion
Tumorigenesis Via Cell Signaling
Tumorigenesis in Response to ROS-Mediated Activation of Factors and Other Genetic Changes
Angiogenesis
Metastasis
Role of ROS in Tumor Suppression
Apoptosis
Autophagy
Necrosis
Ferroptosis
Chemosensitization
ROS in Cancer Stem Cells
Role of ROS in Cancer Therapies
Roles of ROS in Molecular Targeted Therapies
Roles of ROS in Targeted Tyrosine Kinase Therapies
Roles of ROS in Cancer Chemotherapy
Roles of ROS in Radiotherapy
Conclusion
References
67 ROS Modulation on Apical Junctional Complex
Introduction
Metastatic Signaling and ROS Modulation
Tight Junctions and Oxidative Stress
Tight Junctions Proteins
Oxidative Stress, Tight Junctions, and Metastasis
Adherent Junctions and Oxidative Stress
Conclusions
References
68 The Interdependence of Inflammation and ROS in Cancer
Introduction
Overview the Role of Main Cell-Components in TME
The Roles of CAFs and TAMs in TME
Immunosuppressive Cell Types in TME
NK and B Cells in the TME
TME Network
Interdependence of ROS and Inflammation in Cancer
Inflammation-Induced ROS in Cancer
Mechanisms of ROS-Induced Inflammation in Cancer
ROS and Inflammation Promote EMT in Cancer
ROS Mediated Interactions in TME
ROS and CAFs in TME
ROS and TAMs in TME
ROS and MDSCs in TME
ROS and Tregs in TME
Therapeutic Approaches to Remodel the TME
Approaches Targeting ROS in TME
Approaches Targeting the Inflammatory Signals in TME
Approaches Targeting the Immunosuppressive Signals in TME
Perspectives and Conclusion
References
69 Interplay Between Oxidative Stress and Endoplasmic Reticulum Stress in the Metastasis of Colon Cancer
Introduction
Incidence and Risk Factors of Colon Cancer
Stages and Pathological Features of Colon Cancer
Impact of Oxidative Stress on Colorectal Cancer
Endoplasmic Reticulum Stress and Colon Cancer
ER Stress and Colon Cancer
Role of ER Stress in Mediating Epithelial-Mesenchymal Transition
Role of ER Stress in EMT
ER Stress in Cell Fate Decision
Conclusion
References
70 Mitochondria-Targeted Antioxidants and Cancer
Introduction
Antioxidants and Cancer Therapy
Mitochondria and Cancer
Mitochondrial Antioxidant Defense System
Dismutation of Superoxide Radicals
Removal of H2O2
Targeting Mitochondrial Oxidative Stress
Antitumor Effects of Mitochondria-Targeted Antioxidants
MitoQ
SkQs
Mito-Vitamin E
Mitochondrial-Targeted Nitroxides
Mito-Carboxy PROXYL (Mito-CP)
TPP+-Conjugated TEMPO Derivatives
SS Tetrapeptide
Conclusion
Cross-References
References
71 ROS-Mediated Genome Alterations at Cellular Microenvironment During Cancer Metastasis: A Curtain Raiser
Introduction
Aneuploidy: The Key Factor in Tumerogenesis
Effects of Aneuploidy on Cellular Metabolism (Cancer Microenvironment)
Oxidative Stress and Molecular Damage
Nucleic Acids Damage (DNA and RNA)
Role of ROS in DNA Damage by Oncogenic Replication Stress
Protein Damage
Lipid Damage
Conclusion
References
72 Oxidative Stress in Cancer and Its Influence on Amoeboidal Migration
Introduction
Cancer and Cellular Migration
Epithelial Migration
Multicellular Streaming
Tumor Budding
Single Cell Migration
Mesenchymal Migration
Amoeboid Migration
Components of Amoeboidal Migration
Relationship Between Amoeboidal Migration and Oxidative Stress
Oxidative Stress and Migration Plasticity
Mesenchymal to Amoeboid Transition (MAT)
Amoeboid to Mesenchymal Transition (AMT)
Collective to Amoeboid Transition (CAT)
Conclusion
Reference
73 The Intricacy of ROS in Cancer Therapy Resistance
Introduction
Introduction to Reactive Oxygen Species (ROS)
Sources and Activation of ROS
Regulation of ROS Production
ROS Regulating Cancer and Therapy Resistance: Highlighting the Dichotomous Role of ROS
Cancer-Promoting Roles of ROS
Increase Genomic Instability by ROS
Alteration of Metabolic Pathways by ROS
Regulation of Metastasis by ROS
Triggering of Angiogenesis by ROS
Epigenetic Regulation by ROS
Cancer-Killing Roles of ROS
Induction of Apoptosis by ROS
Effect on Cancer Stem Cells by ROS
ROS-Induced Senescence
ROS-Induced Necrosis
ROS-Induced Cell Cycle Arrest
Molecular Pathways Regulated by ROS in the Cancer Therapy Resistance
The Impact of ROS and Antioxidant Defense System to Promote Cancer Therapy Resistance
P-glycoprotein Regulation by ROS to Promote Cancer Therapy Resistance
The Interplay Between Autophagy and ROS in the Development of Cancer Therapy Resistance
Conclusions and Future Perspectives
References
74 Oxidative Stress
Introduction
Free Radicals: Precursors of Oxidative Stress
Oxidative Stress in Breast Cancer
Oxidative Stress in Breast Tumor Growth
Role of Oxidative Stress in Modulation of Breast Tumor Microenvironment
Role of Oxidative Stress in Breast Tumor Metastasis
Role of Oxidative Stress in Breast Tumor Angiogenesis
Role of Oxidative Stress in Metabolic Reprogramming in Breast Cancer
Drug Resistance Due to Oxidative Stress in Breast Cancer
Oxidative Stress and Breast Cancer Therapy
Conclusion
References
75 Relationship Between ROS, Autophagy, and Cancer
Introduction
Reactive Oxygen Species
Signaling by ROS
Autophagy
Initiation
Nucleation
Phagophore Expansion and Maturation
Lysosomal Fusion
Degradation
Signals that Trigger Autophagy
Activation of Autophagy by ROS
Protective Effect of Autophagy Against Ischemia
The Conjugation Complex ATG3, ATG4, ATG7, and ATG8 (LC3)
ROS Induce Transcription Factors of Autophagy Genes
The Transcription Factor EB (TFEB)
Transcription Factors FoxO1 and FoxO3
Activation of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)
c-Jun/c-Fos-Beclin 1
Negative Feedback Against ROS
Hypoxia Inducible Factor HIF1-BNIP3
Autophagy Activating Complexes ATF4/LC3 and CHOP/ATG5
Conclusions
References
76 TRP Channels, Oxidative Stress, and Cancer
Introduction
Present Knowledge of TRP Channels, Cancer, and Oxidative Stress
Altered Expression of TRP Channels and Cancer Pathology
TRP Channels: Tumor Enhancer or Suppressor
TRP Channels, Oxidative Stress, and Angiogenesis
Functional Role of TRP Channels in Cancer Under Oxidative Stress
TRPA1
TRPM2
Advanced Understanding of Redox-Sensitive TRP Channels in Relation to Specific Cancer Pathology
Reactive Electrophiles, TRP Channels, and Lung Cancer
Acute Myeloid Lymphoma (AML) and TRPM2 Channels
Altered Mitochondrial Bioenergetics, TRPM2 Channels and Gastric Cancer
Glioblastoma and TRP Channels
Oxidative Stress, Other TRP Channels, and Their Role in Breast and Prostate Cancer
Involvement of TRP Channels in Other Types of Cancer
Conclusions and Future Directions
References
77 Wnt Signaling in Cancer
Introduction
Wnt Signaling Pathways and Machinery
Wnt Ligands and Receptors
Wnt Canonical Pathway
Noncanonical Wnt Pathways
Aberration in Wnt Signaling in Cancer
Colorectal Cancer (CRC)
Leukemia
Liver Cancer
Lung Cancer
Multiple Myeloma
Ovarian Cancer
Breast Cancer
Other Cancers
Targeting of Wnt Signaling in Cancer Therapeutics
Conclusion
References
78 Two-Faced Role of ROS in the Regulation of Cancer Cell Signaling
Introduction
Significance of ROS in Cancer
Cellular ROS
Oxidant Sources
Oxidant Types
Commanding Role of ROS in Cancer
ROS Regulation
ROS Regulation by the Antioxidant Defense System
Regulation of ROS by Tumor Suppressor Genes
ROS as a Signaling Molecule
Impact of Two-Faced ROS on Cancer Signaling
One Face: ROS Enhances Protumorigenic Signaling in Cancer
Second Face: ROS Regulates Anti-tumorigenic Signaling in Cancer
Conclusion
Cross-References
References
79 Oxidative Stress and Notch Signaling
Introduction
Notch Signaling in Cancer
Oxidative Stress in Cancer
Cross Talk Between Oxidative Stress and Notch Signaling in Cancer
Oxidative Stress Regulated Notch Signaling in Cancer
Notch Signaling Regulates Oxidative Stress in Cancer
Implications of the Cross Talk Between Notch Signaling and Oxidative Stress in Cancer
Proliferation and Survival
Apoptosis
Epithelial to Mesenchymal Transition (EMT), Migration, and Invasion
Cancer Stem Cells (CSCs)
Therapeutic Targeting of Oxidative Stress/Notch Signaling in Cancer
Conclusion
References
80 ROS-Induced Regulatory Crosstalk with Autophagy and AKT/mTOR Signaling in Cancer Cells
Introduction
Understanding ROS-Induced Autophagy Response During Cancer
Relation Between ROS and Autophagy During Malignancy
Specific Signaling Pathways Linking ROS and Autophagy
Impact of ROS-Responsive Autophagy in Chemotherapeutic Applications
Role of ROS-Responsive PI3K/AKT/mTOR Signaling During Cancer
Conclusion
References
81 Redox Regulation of Estrogen Signaling in Human Breast Cancer
Introduction
Estrogen and Breast Cancer
Estrogen Actions by Oxidative Stress-Mediated Signaling
Estrogen Synthesis and Its Metabolizing Pathways
Molecular Mechanism of Estrogen Biosynthesis
Estrogen-Metabolizing Enzymes and Its Receptor
Estrogen Sulfotransferase
Steroid Sulfatase
Receptors
Involvement of SULT1E1 in Breast Carcinogenesis
Involvement of NFκB in Breast Carcinogenesis
Involvement of Nrf-2 in Breast Carcinogenesis
Discussion
Conclusion
References
82 ROS Impacts on Cell Cycle Checkpoint Signaling in Carcinogenesis
Introduction
ROS Impacts on G1 Phase Regulators and Carcinogenesis Risk
G1 Phase Events
G1 Tumor Suppressor Genes and ROS
p14
p53
p21
p27 and p57
RB
TGF-β
G1 Oncogenes and ROS
Mdm-2
CDK4/Cyclin D
CDK2/Cyclin E-A
ROS Impacts on S Phase Signaling Proteins and Carcinogenesis Risk
S Phase Events
S Tumor Suppressor Genes and ROS
p21
ATM and ATR
S Oncogenes and ROS
CDC25A
CDK2/Cyclin A
ROS Impacts on G2 Phase Regulators and Carcinogenesis Risk
G2 Phase Events
G2 Tumor Suppressor Gene and ROS
p21
G2 Oncogenes and ROS
CDC25C
CDK1/Cyclin B
ROS Impacts on M Phase Regulators and Carcinogenesis Risk
M Phase Events
M Tumor Suppressor Genes and ROS
p53
APC/C
M Oncogene and ROS
CDC20
Conclusion and Future Direction
References
83 Modulation of JAK/STAT Pathways in Cancer by Phytochemicals
Introduction
Pathophysiology of Cancer
Phytochemicals and Cancer
JAK/STAT Signaling Pathway in Oncogenesis
Regulation of JAK/STAT Signaling In Vitro by Phytochemicals
Inhibition of JAK/STAT Signaling in Animal Models by Phytochemicals
The Interaction of Phytochemicals Regulating JAK/STAT with Chemotherapeutic Drugs
Conclusion
References
84 Role of Carotenoids on Oxidative Stress-Mediated Signaling in Cancer Cells
Introduction
Oxidative Stress and Cancer
Carotenoids and Cancer
Effect of Carotenoids on Cell Cycle Regulation in Cancer Cells
Role of Carotenoids on Apoptosis Induction in Cancer Cells
Role of Carotenoids on Redox-Sensitive Protein-Mediated Cell Death Progression in Cancer Cells
Effect of Carotenoids on Growth Factors and Regulation of Cell signaling in Cancer Cells
Role of Carotenoids on the Regulation of Cell Signaling
Redox-Related Modulation of Transcription Factors
Conclusion
References
85 Cross Talk Between Oxidative Stress and p53 Family Members in Regulating Cancer
Introduction
Role of p53 Family Members in Genomic Integrity Maintenance Under Oxidative Stress
P53 Family and ROS Cross Talk in Cellular Metabolism
ROS and p53 Family in Cell Death
Conclusion
References
86 Mutant K-Ras-Mediated Oxidative Stress in Pancreatic Cancer
Introduction
K-ras Mutation: The Driving Force of PDAC Tumorigenesis
Oxidative Stress in Pancreatic Cancer
K-rasG12D and Redox Balance in PDAC Cells
Conclusion
References
87 mRNA Stabilizing Factor HuR: A Crucial Player in ROS-Mediated Cancer Progression
Introduction: mRNA Half-life, RNA-Binding Proteins, and Oncology
HuR and Its Nuts and Bolts
HuR Linked in Tumorigenicity and Therapeutics
HuR, the Effective Modulator of ROS Generation in Cancerous Traits
Discussion and Future Directions
References
88 Redox State and Gene Regulation in Breast Cancer
Introduction
Origin of ROS in Cells
ROS Mediated Signaling Pathways
ROS and Breast Cancer
Additional Mechanisms of ROS Generation in Cancer Cells
Modulation of Cancer Pathways by ROS
DNA Damage Response
Epigenetics and Gene Regulation
Alterations in Signaling Pathways
Cellular Proliferation
Cell Survival
Autophagy
Angiogenesis
Motility and Metastasis
Conclusion
References
89 Glutathione Peroxidase and Lung Cancer: An Unravel Story
Introduction
GPX and Its Characterisation
GPX and Its Involving Pathways
GPX and Its Co-expressed and Interacting Genes
GPX and Lung Cancer
Conclusions and Future Direction
References
90 Importance of Silencing RNAs in Cancer Research
Introduction
Silencing RNA (siRNA) in RNA Interference
Concise Introduction About siRNA
Applications of siRNA
SiRNA Mediated Drug Delivery Methods
Narrowing Down to the Intervening Drug Delivery Methods of siRNA Specific to Cancer Treatment
SiRNAs Delivery System for Neurogenerative Disease Conditions
Limitations of siRNA Delivery to the Targeted Site for Actions
Versatility of siRNA Employed for Therapeutic Application of Cancer
Chemical Alterations of siRNA
Lipid Mediated siRNA Delivery System
Polymer-Enhanced siRNA Delivery System
Different Modes of Administration by the Delivery of siRNA
Emphasizing the Systemic Delivery Approaches of siRNA
Conclusion
Future Perspective
Reference
91 Cellular Redox Status and Modifiable Behaviors
Introduction
Excess Body Weight
Poor Nutrition
Cigarette Smoking
Conclusion
Cross-References
References
92 Yin-Yang of Oxidative Stress in Pancreatic Cancers
Introduction
ROS-Induced Epigenetic Regulation in Cancer
DNA Methylation
Histone Modification
Transcriptional Control
Posttranscriptional Control
Translational and Posttranslational Control
MAPK/ERK1/2 Pathway
AKT Pathway
JAK-STAT Pathway
NRF2-KEAP Signaling Pathway
Conclusion
Summary
Cross-References
References
93 Epigenetic Therapy as a Potential Approach for Targeting Oxidative Stress-Induced Non-small-Cell Lung Cancer
Introduction
Etiology of Lung Cancer
Smoking
Genetic Factors
Gender
Age
COPD and Other Pulmonary Conditions
Diet and Obesity
Environmental Air Pollution
Role of Reactive Oxygen Species (ROS) in Lung Cancer
Oxidative Stress-Mediated Non-Small-Cell Lung Cancer (NSCLC)
Role of Cigarette Smoking in Oxidative Stress-Induced LC (NSCLC)
Epigenetic Changes Due to OS in NSCLC
DNA Modification/Mutation and Lung Cancer
HDACi as Potential Epigenetic Therapy in NSCLC
Conclusion
Reference
94 Free Radicals-Mediated Epigenetic Changes and Breast Cancer Progression
Introduction
Epigenetics and Control of Gene Expression
DNA Methylation
Histone Modifications in Epigenetic Regulation
Noncoding RNAs (Long Noncoding RNA and MicroRNAs) and ATP-Dependent Chromatin Remodeling Complexes in Epigenetic Regulation
Biology of Breast Cancer
Oxidative Stress, Reactive Oxygen Species (ROS) Generation, and Epigenetic Mechanisms in Breast Cancer
Free Radicals in Health and Cancer
Free Radicals Induced Epigenetic Alterations and Affected Pathways
Antioxidant Enzymes and Redox Homeostasis
ROS-MicroRNAs Interactions and Epigenetic Alterations in Breast Cancer
Oxidative Stress in Breast Cancer Epigenetics, and Scope of Treatment
Dietary Agents with Antioxidant Properties as Epigenetic Modulators in Breast Cancer
Curcumin
Resveratrol
Quercetin
The Interplay Between Oxidative Stress and Epigenetic Drugs in Breast Cancer
Conclusive Remarks
Cross-References
References
95 Phytochemicals in ROS-Mediated Epigenetic Modulation of Cancer
Introduction
Epigenetic Control Mechanisms in Cells
Histone Modification
DNA Methylation
Epigenetic Control by microRNA
Oxidative Stress and Inflammation
Keap1-Nrf2 Pathway
Epigenetic Control by Phytochemicals
Roles of Phytochemicals in Epigenetic Regulation
Conclusion
References
96 Noncoding RNAs Regulation of Redox Balance in Cancer
Introduction
MiRNAs Regulation of Redox Homeostasis in Cancer
Breast Cancer
Classical Hodgkin Lymphomas
Colon Cancer
Colorectal Cancer
Gastric Cancer
Glioma
Hepatocellular Carcinoma
Lung Cancer
Medulloblastoma
Neuroblastoma
Oral Carcinoma
Ovarian Cancer
p53 Wild-Type Cancers
Pancreatic Cancer
lncRNAs Regulation of Redox Homeostasis in Cancer
snoRNA Regulation of Redox Homeostasis in Cancer
circRNA Regulation of Redox Homeostasis in Cancer
Conclusion
References
97 Oxidized DNA Base Damage Repair and Transcription
Introduction
Oxidative DNA Base Damage Shaping the Mutation Burden in Cancer
Oxidative DNA Base Damage Repair
The Interplay Between Posttranslational Modification of BER Proteins and Transcriptional Regulation
8-OxoG and OGG1 as a Novel Epigenetic Regulator for Controlling Gene Expression
BER in Hypoxia-Induced VEGF mRNA Expression
Role of 8-OxoG and OGG1 in the Regulation of Inflammatory Response Genes
Histone Demethylation, Oxidation of DNA, BER, and Gene Expression
Regulatory Roles of G Oxidation and BER Proteins in G4 Structure Formation in the Genome to Regulate Gene Expression
Conclusion
References
98 Epigenetic Instability Caused by Oxidative Stress Triggers Tumorigenesis
Introduction
Oxidative Stress-Induced Epigenetic Changes
Role of Oxidative Stress in Regional Hypermethylation in the Promoter Region of TSGs
Oxidative Stress-Induced Global Hypomethylation
Therapeutic Strategies to Regulate Epigenetic Alterations
Polyphenols
HDAC or DNMT Inhibitors
Histone Deacetylase Inhibitors (HDi)
Nuclear Factor Erythroid 2-Related Factor 2 Inhibitors
Conclusion and Future Directions
Cross-References
References
99 Implications of ROS in Cancer Stem Cells Mechanism of Action
Introduction
CSCs Inside Stem Cells Spectrum
CSCs Heterogeneity and Metabolic Landscape
Plasticity, Quiescence, and Embryonic Signature of CSCs
Tumor Microenvironment: CSC Relationship
The Signaling Pathways Involved in CSCs Maintenance
ROS, Carcinogenesis Theories, and CSCs
Oxidative Stress in Cancer Initiation and Development
Direct Damage of Structural Components and Metabolism with Induction of Gene Mutations
Modulation of Signal Transduction Pathways or Gene Transcription Factors with Alterations of Oncogene Expression and Tumor Pro...
The Association Between Oxidative Stress and CSCs
Single Nucleotide Polymorphisms Results in Cancer Risk Increase
Pathologic Conditions Related to Oxidative Stress and Carcinogenesis Promoters
ROS and Tumor Status
CSCs and Metastasis
Conclusions
References
100 Metabolism-Redox Interplay in Tumor Stem Cell Signaling
Introduction
Cancer Stem Cell Signaling
Cancer Stem Cell Metabolism
Redox Regulation in Cancer Stem Cells
Intracellular Signaling - Redox State Crosstalk: Metabolism Interplay
Conclusions
Cross-References
References
101 Association of ROS with Epithelial-Mesenchymal Transition and Acquisition of Stemness During Carcinogenesis
Introduction
Epithelial-Mesenchymal Transition
What Is EMT?
Types of EMT
Type-1 EMT
Type-2 EMT
Type-3 EMT
EMT and Cytoskeleton
Transcriptional Regulation of EMT
EMT and Carcinogenesis
Invasion-Metastasis Cascade
Step-1: Invasion
Step-2: Intravasation
Step-3: Extravasation
Step-4: Colonization
EMT and Cancer Stem Cells
Oxidative Stress: Regulator of EMT and CSC
What Is Oxidative Stress?
ROS and EMT
Redox Regulation over EMC Remodeling
ROS and Cytoskeletal Rearrangement
Oxidative Stress and Cell-Cell Junction Regulation
Redox Regulation over Cell Mobility
Association of ROS with EMT and Stemness
Differential Level of ROS in CSCs and Non-CSCs
Conclusion
References
102 Therapeutic Effect of Natural Compounds in Targeting ROS-Induced Cancer
Introduction
Natural Compounds in Regulation of ROS Generation
Polyphenols
Flavonoids
Proanthocyanidins
Anthocyanidin or Anthocyanin
Flavones
Isoflavones
Flavonol
Flavan-3-ol
Flavanone
Nonflavonoids
Stilbenes or Stillbenoid
Phenolic Acid
Hydroxycinnamic Acids and Hydroxybenzoic Acids
Flavonolignans
Coumarins
Lignans
Other Polyphenols
Diarylheptanoid
Curcumin
Vitamins
Carotenoid (Vitamin A or Retinol, Fucoxanthin)
Vitamin C
Dehydroascorbic Acid (DHA)
Vitamin E
Vitamin K3
Alkaloids
Sampangine
Boldine
Quinoline
Pyridocarbazole
Isoquinoline
Terpenoids
Triterpenoid
Lactone Sesquiterpenoid
Saponins
Carotenoid
Diterpenoids
Quinones
Cribrostatin 6
Naphthoquinone
Thymoquinone
Toluquinones
Miscellaneous Natural Compounds and Products
Essential Oils (EOs)
Boswellia Carteri (Frankincense Oil) EO
Artemisia Lavandulaefolia EO
Salvia Libanotica EO
Boswellia Sacra EO
Aniba Rosaeodora (Rosewood) EOs
Zanthoxylum Schinifolium EO
Minerals
Zinc
Selenium
Isothiocyanates
BITC
PEITC
Sulforaphane
Conclusion
References
103 Therapeutics of Oxidative Stress and Stemness in Breast Cancer
Introduction
Oxidative Stress, Tumor Heterogeneity, and Cancer Progression
Role of NO in Stem Cells and DNA Damage Response
Role of ROS in Cancer Cells
Role of Oxidative Stress in Evolving Cancer Cells
Role of Oxidative Stress in Microenvironment
Therapeutic Targeting of Oxidative Stress
Future Directions
Conclusion
Cross-References
References
104 Reactive Oxygen Species in Stem Cell Proliferation and Cancer
Introduction
Stem Cells and Their Classification
Types of Stem Cells
Reactive Oxygen Species
Role of Reactive Oxygen Species (ROS)
Chemistry of Reactive Oxygen Species
Cellular Generation of ROS
Role of ROS in Cell Proliferation
Signaling Through Cell Cycle
Role of Hypoxia in Induction of Proliferation
Hypoxia/ROS in Stem Cell Differentiation
Cancer Stem Cells (CSCs)
Development of Cancer from CSCs
ROS-Dependent Signaling Pathways in CSCs
Antioxidant Mechanism of ROS Scavenge
ROS-Associated Diseases Through Lifestyle
Conclusion
References
105 Targeting Redox Signaling and ROS Metabolism in Cancer Treatment
Introduction
Generation, Pathophysiological, and Regulatory Functions of Reactive Oxygen Species
Sources of ROS
ROS in the Regulation of Physiological and Pathophysiological Signal Transduction Pathways
Excess ROS Perturbs the Cellular Homeostasis
Reactive Oxygen Species and Cancer
ROS in Cancer Progression
ROS in Cancer Inhibition
Application of ROS Induction for Anticancer Strategies
Direct ROS Generation
Antioxidant Process Inhibition
Combination Therapy
Immunotherapies
Conclusions and Future Direction
References
106 Modulatory Role of Adipocytes and Their Stem Nature in the ROS Signaling Within a Tumor Micro-environment
Introduction
Lipid and ROS-Signaling in the Adipocyte-Mediated Tissue Dynamics?
Conjugated Linoleic Acids as Switching Molecules
Mechanism of CLA-Induced Delipidation/Dedifferentiation in the Adipocyte
Role of ROS in the CLAs Switching Mechanism
The Role in Cancer
Conclusions
References
107 Hypoxia-Induced Stress Responses in Cancer and Cancer Stem Cells
Introduction
HIF-1α a Key Player in Tumor Hypoxia
Metabolic Adaptation to Hypoxia
Antioxidative Responses
ER-Stress Response to Hypoxia
Autophagy
Hypoxia and Cancer Stem Cells (CSCs)
Hypoxia and Cancer Therapy
Conclusion
References
108 Oxidative Stress-Targeted Therapies for the Treatment of Acute Myeloid Leukemia
Introduction
Oxidative Stress Targeted Therapies
Prooxidant Therapy
Antioxidant Therapy
ROS-Mediated Differentiation Therapy
Conclusion
Cross-References
References
109 Role of ROS in Cancer Stem Cells
Introduction
Stem Cells and Their Role in Cancer
Cancer Stem Cells
Biomarkers of Ovarian CSCs
Surface Markers
Functional Markers
Ovarian CSC Microenvironment
Growth Factor-Mediated Proliferative Signaling
Cytokines and Inflammatory Network
miRNA Mediated Stemness Maintenance
Effect of ROS on Cancer Stem Cells: Avenues for Therapy
Stem Cells and ROS
Reactive Oxygen Species in Cancer and Cancer Stem Cells
Regulation of ROS in Malignancy and CSCs
ROS-Dependent Fundamental Transcription Factors in CSCs
HIF-1α
NF-kB
p53
NRF2
ROS-Dependent Fundamental Signal Transduction Pathways
ATM Pathway
PI3K/AKT Pathway
PTEN
FOXOs
Notch Pathway
Wnt Pathway
Clinical Relevance of CSCs
Recent Developments (Drug Candidates)
Conclusion
References
110 Reactive Oxygen Species-Dependent Signaling Pathways in Cancer Stem Cells
Introduction
Cancer Stem Cells
ROS-Mediated Signaling in CSCs
Ataxia Telangiectasia Mutation (ATM) Pathway in CSCs
PI3K/AKT Pathway in CSCs
Notch Pathway in CSCs
Wnt Pathways in CSCs
STAT Pathway in CSCs
ROS-Dependent Transcription Factors in CSCs
Hypoxia Inducing Factor (HIF) in CSCs
NF-κB in CSCs
Tumor Suppressor p53 in CSCs
The Nuclear Factor Erythroid 2-Related Factor (Nrf2) in CSCs
Role of ROS in Epithelial-Mesenchymal Transition in CSCs
CSCs and Drug Resistance
Conclusion
References
111 System Biology and Network Analysis Approaches on Oxidative Stress in Cancer
Introduction
Relation Between Hypoxia and ROS in Development and Progression of Cancer
Computational Systems Biology in Revealing Complex Molecular Interconnectivity Network in Cancer
In Silico Approaches in Oxidative Stress-Induced Cancer
Construction of Disease-Specific Interaction Network
Identification of IIP and Bottlenecks
Construction of Signaling to Metabolic Crosstalk Pathway and Connectivity Analysis
Discussion
Conclusion
Cross-References
References
112 Reactive Oxygen Species–Mediated Cancer Progression and Metastasis
Introduction
Involvement of ROS in Progression and Metastasis of Cancer
Sources of ROS in Cancer Cells
Mechanisms Involved in ROS-Mediated Cancer Progression and Metastasis
Botanicals Inhibit Cancer Progression and Metastasis
Conclusion
References
113 Anthocyanins and Flavonols: Therapeutic Implications of Natural Compounds on Cancer
Introduction
Anthocyanins and Anthocyanidins: General Overview
Cyanidin and Cyanidin-3-O-Glicoside
Delphinidin and Delphinidin-3-O-Glucoside
Flavonols: General Overview
Kaempferol
Quercetin
Conclusion
References
114 Implication of Nanomedicine in Therapy of Oxidative Stress-Induced Cancer
Introduction
ROS and Cancer
ROS and Its Biological Functions
Role and Mechanism of ROS in Cancer Development
ROS Induced Transcription Factor and Regulation
ROS Altered Biomolecules Functions
Oxidative Stress Adaptation in Cancer
Therapeutics Targeting Oxidative Stress Alteration in Cancer
Nanoparticulate Carriers
Nanovesicular Carriers
Liposomes
Micelles
Nanoemulsions
Conclusion
References
115 Metabolic Oxidative Stress in Initiation, Progression, and Therapy of Cancer
Introduction
Metabolic Reprogramming and Cancer
Metabolic Reprogramming and Enhanced Glycolysis
Metabolic Reprogramming and Altered Cell Signaling
Subcellular Organelles Adaptation to Metabolic Reprogramming
Metabolic Oxidative Stress in Cancer Cells
Molecular Drivers of Metabolic Oxidative Stress
Reactive Oxygen Species in Cancer
Glucose Metabolism and Oxidative Stress
Antioxidant Defense against Metabolic Oxidative Stress
Metabolic Oxidative Stress, Tumor Growth and Metastasis
Metabolic Oxidative Stress and Drug Resistance
Modifiers of Metabolic Oxidative Stress
Modifiers of Tri Carboxylic Acid (TCA) Cycle
Modifiers of Glutamine Metabolism
Modifiers of Pentose Phosphate Pathway (PPP)
Modifiers of Serine-Glycine One-Carbon (SGOC) Metabolism
Modifiers of Glycolytic Pathway
Inhibitors of Redox Regulating Proteins
Inhibitors of Glycolysis (2-Deoxy-D-Glucose) and Oxidative Stress
Clinical Applications/Implications
Pro-oxidants and Combinational Therapies
Antioxidants and Combinational Therapies
Limitations of Metabolic Oxidative Stress Targeting Agents or Drugs/Therapeutics and Strategies for Improving Efficacy
Conclusion
References
116 Mitochondrial ROS: A Reactive Species Targeted in Cancer Therapy
Introduction
ROS
Mitochondria Produce ROS
Tight Modulation of Mitochondrial ROS
Physiological Targets of ROS
Mitochondrial ROS Act as Signaling Molecules
Physiological mROS in Cellular Regulation
Cell Proliferation During Hypoxia
mROS During Angiotensin II Signaling
mROS in Cancer Cells Proliferation
Mitochondrial Antioxidant Systems
SOD2/MnSOD2
GPx-1 and GPx-4
Prx3/TrxR2/Trx2
Targeting mROS in Cancer Therapy
Conclusion and Future Perspective
References
117 Oxidative Stress and Hypoxia in Cancer: Implications for Radiation Therapy
Introduction
Reactive Oxygen Species (ROS) and Oxidative Stress
Cellular Origin of ROS
The ROS Detoxifying Systems
Effect of ROS
ROS and Cell Proliferation
ROS and Cell Death
ROS and Metabolic Remodeling of Cancer Cell
ROS and Metastasis
Hypoxia
Effects of Hypoxia on Tumor Progression
The Effect of Metabolic Remodeling by Hypoxia
Maintaining the Anabolic Flux Through High Glycolysis
Hypoxia and HIF
HIF-1 and Tumor Progression
HIF-1 and Metabolic Remodeling
HIF-1 and Regulation of ROS Production by Cancer Cells
Oxidative Stress, Hypoxia, and RT
Manipulation of ROS Homeostasis, Hypoxia-Affecting Factors, and Tumor Hypoxia for Improving RT Response
Manipulation of ROS Homeostasis
Manipulation of Factors Affecting the Tumor Hypoxia
Manipulation of Tumor Hypoxia
Conclusions
Cross-References
References
118 Oxidative Stress in Cancer
Introduction
Inorganic Selenium and Its Implecation in Cancer Prevention and Therapy
Anticancer Potential of Organoselenium Compounds
Heterocyclic Se-Compounds
Organoselenocyanate
Isoselenocyanate
Methylseleninic Acid (MSC)
Nanoformulted Se-NPs Based Cancer-Therapy
Se-NPs as Carrier for the Anti-Cancer Drug Delivery
Conclusion and Expert Opinion
References
119 Phytocompounds-Based Approaches to Combat Oxidative Stress in Cancer
Introduction
Oxidative Stress in Cancer and Its Modulation by Phytocompounds
Phytocompounds-Based Therapeutic/Preventive Approach for the Oxidative Stress-Induced Cancer
Flavonoids
Kaempferol
Biochanin-A
Luteolin
Triterpenoids
Lupeol
Betulinic Acid
Oleanolic Acid
Ursolic Acid
Cucurbitane
Phytoestrogens (Daidzein and Genistein)
Conclusion
References
120 Phytoestrogens Modulate Oxidative Stress
Introduction
Phytoestrogen Structure and Classification
Shared Mechanisms of Estrogens and Phytoestrogens
Phytoestrogens as Cancer Treatment
Concluding Remarks
Cross-References
References
121 Prospective Application of Natural and Synthetic Redox Modulators in Oxidative Stress-Targeted Cancer Therapy
Introduction
ROS-Manipulation Strategies in Cancer Treatment
ROS-Depleting Strategy in Cancer Treatment
ROS-Elevating Strategy in Cancer Treatment
Combination Therapy
Conclusion
References
122 ROS Modulation by Iron Chelators and Lipids: A Developing Anticancer Strategy
Introduction
Cancer Metabolism and Its Link with ROS Production
Cancer Is Caused by Genomic Instability but Also by Biophysical and Chemical Changes
Cancer Metabolism
The Unique Bioenergetics of Cancer Cells
Cancer Metabolism and Bioenergetics and Their Relation to ROS Production
ROS in Cancer
Iron, ROS Production, and Iron Chelators
Iron Chelators as Anticancer Agents
Fe Chelators: ROS Scavengers or Proliferation Inhibitors?
Iron Chelators and ROS Production
Cancer Cell Iron Addiction and Iron Chelation
ROS Modulation by Lipids as an Anticancer Strategy
Membranes of Cancer Cells
Membranes (General)
Phosphatidylcholine (PC)
Phosphatidic Acid (PA)
Phosphatidylethanolamine (PE)
Lipid Droplets (LD)
Biophysics of Membranes
Importance of Membrane Functions
Membranes in Cancer
ROS Production and Lipids
Lipids as Antioxidants: Vitamin E
Lipids as Antioxidants: 2-Hydroxyoleic Acid (2OHOA)
Conclusion
Cross-References
References
123 ROS, Cancer, Stem Cells
Introduction
Functional Significance of ROS in Cancer Cells
Does Antioxidants Ameliorate Cancer Progression?
Does Prooxidants Promote Killing of Cancer Cells?
Factors Affecting ROS-Induced Cancer Progression
ROS-Induced by Non-targeted Cancer Therapies
ROS-Induced by Targeted Cancer Therapy
Dynamic Role of ROS in Cancer Stem Cells
The beneficial and harmful ROS in Cancer
Conclusions and Viewpoints
Cross-References
References
124 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
Clinical Trials of NF-κB/ROS Signaling Modulators
Conclusions
Cross-References
References
125 Hyperglycolysis-Inflammation Connect as a Mechanistic Hot Spot in Oxidatively Compromised Cancer
Introduction
Searching Hot Spots from Tumor Cell Metabolism
Tumor Cell ROS Metabolism as a Poor Mechanistic Target
The Hyperglycolysis and the Tumor Growth
The Key Glycolytic Players
Hexokinases
Phosphofructokinases: PFK1 and PFK2
Pyruvate Kinase M2
Lactate Dehydrogenase (LDH)
M4-LDH: Cancer-Related Inflammation and Tumor Microenvironment
Epithelial-Mesenchymal Transition (EMT) and the Process of Metastasis and Angiogenesis
Tumor-Associated Macrophages (TAMs): Negotiator Between the Cancer Cell and Tumor Matrix
TME and TAM Suppress Tc Cell Activation Against the Tumor Cells
TAM, TME, and Angiogenesis
Major Hot Spots in the Hyperglycolysis-Inflammation Connect
Conclusion
References
126 Constraint-Based Modeling to Understand ROS-Mediated Effects in Cancer
Introduction
Constraint-Based Modeling (CBM) Principle and Methodology
Genome-Scale Metabolic Models (GSMMs)
Mathematical Representation of GSMM
COBRA Toolbox
Flux Balance Analysis (FBA)
Flux Variability Analysis (FVA)
Context-Specific Metabolic Models Reconstruction and Analysis
Context-Specific Metabolic Model Generation
Cancer-Specific Metabolic Reconstructions to Model Cancer Metabolism
PAN Cancer Analysis of Human Metabolic Reconstruction
Retinoblastoma GEM
Prostate Adenocarcinoma-Specific Metabolic Model
Hepatocellular Carcinoma GEMs
Colon Cancer-Specific Metabolic Models
Scope of CBM in Studying the Role of ROS in Cancer Treatment and Prevention
Conclusion
References
127 Dynamical Methods to Study Interaction in Proteins Facilitating Molecular Understanding of Cancer
Introduction
Importance of Protein-Protein Interaction (PPI) for the Molecular Understanding of Function
Dynamics Are Key in Determining PPIs
Methods to Recover Protein Dynamics
Dynamics Analysis of Proteins by Molecular Dynamics Simulations
Normal Mode Analysis: An Approach to Recover Native Dynamics of Proteins
Application of Advanced Dynamical Techniques in Cancer-Related Proteins: A Case Study of CDK2
Protein-Protein Binding Inhibition Using Advanced MD Simulations
Normal Mode Analysis for Protein-Protein Complex Elucidating Conformational Change
Conclusion
References
128 Molecular Insights into the Roles of E3-Ligases in ROS-Mediated Cancer from a Bioinformatics Perspective
Introduction
E3-Ligases
RING E3-Ligases
HECT E3-Ligase
RBR E3-Ligase
Reactive Oxygen Species
Ubiquitin Proteasomal System (UPS) and ROS
Role of ROS and E3 Ubiquitin Ligase in Cancer
System Biology and Computational Aspects
Conclusion
Reference
129 Insulin Resistance and Cancer
Introduction
Insulin
Insulin Signaling
Insulin Resistance
Insulin Resistance and Oxidative Stress
Insulin Resistance and Hyperinsulinemia
Cancer
Clinical Findings
Obesity, Prediabetes, and Type 2 Diabetes
Cancer and Diabetes Therapies
Conclusion
Cross-References
References
130 Meprins: Ancient Enzymes Newly Discovered in Cancer Progression
Introduction
Historical Background and General Enzyme Characteristics
Structure of Meprins
Primary Structure
3D Structure of Meprins
Domains and Oligomeric Structure
Meprins and Disease
Catalytic Properties
Meprins and Drug Design
Future Perspectives
References
131 Molecular Analysis of the Involvements of lncRNA in Cancer Development
Introduction
Bladder Cancer
Brain Cancer
Breast Cancer
Colorectal Cancer
Gastric Cancer
Lung Cancer
Osteosarcoma
Ovary Cancer
Prostate Cancer
Analyses of Cancer Associated lncRNAs from a Bioinformatics Point of View
Conclusion
References
132 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
Immuno-sensors 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
Capillary Electrophoresis
Ion Mobility Spectrometry
DI-MS
MALDI-MS
Direct Analysis in Real Time (DART)-MS
Mass Spectrometry Imaging
Challenges and Opportunities
Conclusions
References
133 Systems Biology and Bioinformatics Insights into the Role of Free Radical-Mediated Oxidative Damage in the Pathophysiology...
Introduction
Computational Approaches in Systems Biology
Artificial Intelligence (AI) Predicting Cancer Susceptibility Based on Redox Data
Artificial Intelligence (AI) Predicting Cancer Prognosis Based on Redox Data
Artificial Intelligence (AI) Predicting Therapeutic Outcome Based on Redox Data
Bayesian Networks
Boolean Networks
Multi-omics Analysis
Network Analyses Showing Association of Redox Proteome with Cancer Susceptibility
Network Analyses Showing Association of Redox Proteome with Cancer Prognosis
Network Analyses Showing Association of Redox Proteome with Cancer Therapy
Conclusions
References
134 Systems Biology Resources and Their Applications to Understand the Cancer
Introduction
Systems Biology Databases Used in Cancer Research
Expression and Variation Databases
Immune System and Personalized Medicine Databases Used in Cancer Drug Designing
Databases Used for Interaction and Pathway Analyses
Tumor Databases Used for Drug Designing in Experimental and Clinical Studies
Systems Biology Approaches and Tools to Cancer
Expression and Variation-Based Systems Biology Tools and Approaches for Cancer Prediction
Common Immunoinformatic and Bioinformatics Tools to Cancer Drug Discovery
Biomolecular Networks Tools in Cancer
Text Mining Tools Used in Cancer Research
Mathematical Modeling and Simulation Tools to Model Cancer Pathways and Networks
Clinical Applications of Systems Biology Tools and Approaches
Conclusion
References
135 Targeting Reactive Oxygen Species Homeostasis and Metabolism in Cancer Stem Cells
Introduction
ROS and Cancer Stem Cells
Cross Talk Between Signaling Pathways and ROS in CSCs
PI3K/AKT/mTOR Pathway
Notch Pathway
Wnt Pathway
JAK-STAT Pathway
Metabolic Control of ROS in CSCs
Glucose Metabolism
Lipid Metabolism
Amino Acid Metabolism
Therapeutically Targeting ROS Dynamics in CSCs
Conclusion and Perspective
References
136 Thioredoxin and Glutathione Systems
Introduction
ROS and Redox Control Systems
Glutathione and Thioredoxin Systems in Cancers
Targeting Antioxidant Systems for Cancer Therapies
Conclusions
Cross-References
References
137 Vitamin C in Cancer Management: Clinical Evidence and Involvement of Redox Role
Introduction
Physiological Redox Functions
Role in Cancer Prevention
Role in Cancer Treatment: Clinical Evidence
Mechanisms: Redox Role
Conclusion
References
138 Oxidative Stress, Inflammasome, and Cancer
Introduction
Free Radicals in Oxidative Stress
Classes of ROS
Superoxides (O2-)
Hydrogen Peroxide (H2O2)
Hydroxyl Radical (OH)
Reactive Nitrogen Species (RNS)
Oxidative Stress and Cell Signaling
Oxidative Stress and Inflammasome
Inflammasomes and Cancer
Proliferation and Survival
Immunosuppression
Angiogenesis
Metastasis
Polyphenols
Conclusion
References
139 Preventive Role of Carotenoids in 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
Conclusion
References
140 Personalized Vaccine as a Therapeutic Approach Toward Cancer
Introduction
Genome as a Target for Personalized Cancer Vaccine
Personalized Cancer Immunotherapy
microRNAs (miRNAs) in Personalized Radiotherapy
Conclusion
References
141 Enolase
Introduction
Structure of Enolase
Enolase Isoforms
Enolases and ROS
Enolases and Stem Cells
Enolases and Cancer
Conclusions
Cross-References
References
142 Analytical and Omics Approaches in the Identification of Oxidative Stress-Induced Cancer Biomarkers
Introduction
Cancer Relation with Oxidative Stress
Types of Biomarkers
Diagnostic Biomarkers
Predictive Biomarkers
Prognostic Biomarkers
Therapeutic Biomarkers
Omics Approaches in the Identification of Biomarkers
Genomics
Epigenomics
Transcriptomics
Proteomics
Metabolomics
Analytical Platforms for Biomarker Identification
NMR-Based Approach for Biomarker Identification
MS-Based Hyphenated Techniques for Biomarker Identification
LC-MS Based Approach for Biomarker Identification
GC-MS Approach for Biomarker Identification
CE-MS Approach for Biomarker Identification
Clinically Significant Biomarkers in Oxidative Stress-Induced Cancer
Malondialdehyde (MDA)
8-Hydroxy-2-Deoxyguanosine (8-OHdG)
Isoprostanes
Enzymatic Antioxidants
Chromogranin A
Lysozyme
MicroRNAs (miRNAs)
Challenges Associated with the Cancer Biomarkers Identification
Conclusion
References
143 Reactive Oxygen Species in Cancer Stem Cell Tumorigenesis, Metastasis, and Treatment Resistance
Introduction
ROS Signaling Pathways
PI3K/Akt/mTOR Signaling
Wnt Signaling
MAPK Signaling
STAT3 Signaling
TGF-β Signaling
ROS Transcription Factors
Hypoxia Inducible Factors
Nuclear Factor Erythroid 2-Related Factor 2
Nuclear Factor Kappa B
Nanog
ROS and Oncogene Activation in CSCs
RAS Oncogene
MYC Oncogene
ROS and Anticancer Treatment Resistance
Radioresistance
Chemoresistance
ROS-Dependent Antitumor Strategies
Conclusion
References
144 Dynamics of Cobalt Oxide Nanoparticles in the Activation of Reactive Oxygen Species-Induced Inflammation and Immunomodulat...
Introduction
Nanoparticles and Nanotechnology
Application of Engineering in Medication
Nanoparticle Induced ROS Mediated Inhibition of Cancer
Cobalt Oxide Nanoparticles for Cancer Therapy
Surface Modification Reduces the Toxicity of Cobalt Oxide Nanoparticles
Mechanism of Surface-Modified Cobalt Oxide Nanoparticles on Cells
Surface Modified Cobalt Oxide Nanoparticles Are Potent Immune Stimulator
Cobalt Oxide Nanoparticles Are Potent Antigen Delivery Vehicle
Adjuvanticity of Cobalt Oxide Nanoparticles
Cobalt Oxide Induced ROS Augment Immunostimulation
Conclusions
References
145 Mechanism of Gallic Acid Anticancer Activity Through Copper-Mediated Cell Death
Introduction
DNA Damage Induced by Gallic Acid in Intact and Permeabilized Cells
Determination of DNA Damage by Gallic Acid Along with Metal Chelators in Intact and Permeabilized Cells
H2O2 Generation by Gallic Acid Inside Incubation Medium
Determination of Cell Growth by Gallic Acid in Human Breast Cancer Cells
Gallic Acid and Cancer Chemoprevention
A Copper-Dependent Anticancer Mechanism
Conclusion
Future Direction
References
146 Nitrogen- and Sulfur-Containing Heterocycles as Dual Anti-oxidant and Anti-cancer Agents
Introduction
Thiazoles and Isothiazoles
Benzothiazoles and Other Hybrids
Thiazolidine and Their Derivatives
1,3,4-Thiadiazoles and 1,2,3-Dithiazoles
Thiazines and Benzothiazines
Saccharin-and Acesulfame-Based Anti-Cancer Agents
Phenothiazines
S-Methyl-Isothiosemicarbazones and Their Ruthenium Complexes as Molecular Simplification Products
Thiazepines
Natural Compounds
Conclusion
References
147 Retinoids and Reactive Oxygen Species in Cancer Cell Death and Therapeutics
Introduction
Natural Retinoids Impact on ROS
Synthetic Retinoids Impact on ROS
Conclusion
References
148 Impact of ROS on Cancer and Stem Cell Growth and Therapeutics
Introduction
Reactive Oxygen Species in Cancer Cells
Stem Cells
Origin and Hierarchy of Stem Cells
Embryonic Stem Cells (ESCs)
Adult Stem Cells
Induced Pluripotent Stem Cells (iPSCs)
Cancer Stem Cells (CSCs)
Origin of Cancer Stem Cells
Interplay Between Signaling Pathways and ROS in Cancer and Stem Cells
Oxidative Stress in Somatic Reprogramming
Therapeutics of ROS Induced Cancer and Cancer Stem Cells
Stem Cells, Tissue Engineering and Oxidative Stress
Conclusion
References
Index
