Essential and Non-essential Metals: Carcinogenesis, Prevention and Cancer Therapeutics (Molecular and Integrative Toxicology)

This book aims to present current state of understanding of the role of metals in human health and disease. As it will be difficult to cover all of the metals, about two scores of them, the authors will instead provide a detailed analysis of a select set of essential (__Calcium, Magnesium, Selenium, Iron, copper and Zinc) and non-essential metals (Nickel, Chromium, Cadmium and Arsenic, Tungsten and Asbestos__). Each chapter will have a dedicated section focusing on the binary role that some of these metals play, their carcinogenic and cancer therapeutics, by integrating epidemiological, experimental evidence with special emphasis and focus on molecular mechanisms involved in these processes. The biological analysis will also include emerging lines of evidence such as micro RNAS, kinase families, receptors, endoplasmic, mitochondrial players and epigenetics. As part of integrating the human, experimental and mechanistic data, as well as a detailed analysis into the modes of action for different cancer outcomes will be discussed in each chapter wherever deemed feasible. These approaches are ones in which no other book in this area has attempted to do. Preface 6 Acknowledgements 7 Contents 8 Contributors 9 Chapter 1: Calcium Channels and Pumps: Importance During Lactation as Potential Targets for Breast Cancer 11 1.1 Introduction 12 1.2 Ca2+ Transport Mechanisms in Epithelial Cells 13 1.3 Lactation 15 1.4 Ca2+ Transport During Lactation 15 1.4.1 Basolateral Ca2+ Influx in Mammary Epithelial Cells During Lactation 16 1.4.2 Ca2+ Secretion from Mammary Epithelial Cells During Lactation 18 1.4.3 Ca2+ Efflux from Mammary Epithelial Cells During Lactation 19 1.5 Breast Cancer 20 1.6 Ca2+ Signaling and Transport and Breast Cancer 20 1.6.1 ORAI1 and Breast Cancer 21 1.6.2 SPCA2 and Breast Cancer 22 1.6.3 PMCA2 and Breast Cancer 22 1.7 Summary 23 References 24 Chapter 2: Tumor Development Through the Mg2+nifying Glass 28 2.1 Introduction 28 2.2 Magnesium and Carcinogenesis 29 2.3 Magnesium and Primary Tumor Growth 31 2.4 Magnesium and Tumor Metastasis 33 2.5 Magnesium and Cancer Therapy 35 2.6 Involvement of the TRPM7 Cation Channel 38 2.7 Conclusion 41 References 42 Chapter 3: Selenium: Roles in Cancer Prevention and Therapies 48 3.1 Selenium Is an Essential Element for Animals, and Selenium Deficiency Is Associated with Multiple Diseases 49 3.2 Naturally Occurring Selenium Compounds in Diet and Selenium in Supplements 50 3.3 Cellular Metabolism of Selenium: Transport, Incorporation, Methylation, and Glutathiolation 51 3.3.1 Selenium Uptake 51 3.3.2 Incorporation to Selenoproteins 52 3.3.3 Reduction and Conjugation of Selenium with GSH 52 3.3.4 Methylation of Selenium 52 3.4 Selenoproteins and Their Expression and Function in Cancers 53 3.4.1 Selenoprotein Cellular Function 53 3.4.2 Roles of Selenoproteins in Cancer 55 3.5 Association of Selenium Level/Selenoprotein SNPs with Cancer Pathologies 58 3.6 Clinical Application of Small Selenium Compounds in Cancer Prevention and Treatment 60 3.6.1 Selenium Compounds Applied in Cancer Prevention and Treatment as Antioxidant 60 3.6.2 Small-Molecule Selenium Compounds Used in Cancer Prevention and Therapies 61 3.7 Regulation of Oncology Signals by Selenium Compounds 63 3.7.1 Inorganic Selenite Signaling 63 3.7.2 Selenomethione (SeMet) Action in Cancer Cells 64 3.7.3 Se-Methyl-selenocysteine (Se-MSC) Action in Cancer Cells 65 3.7.4 Methylseleninic Acid (MSA) Action in Cancer Cells 66 3.8 Perspectives: Future of Selenium Application in Cancer 66 References 67 Chapter 4: Zinc and Zinc-Dependent Proteins in Cancer and Chemotherapeutics 78 4.1 Introduction 79 4.2 Zn Homeostasis and Dysregulation 81 4.2.1 Zn Transporters 81 4.2.2 Metallothionein 83 4.2.3 Role of Zn Homeostasis in Chemotherapeutics 84 4.3 Proteins Containing Catalytic Zn 85 4.3.1 Matrix Metalloproteinases 85 4.3.2 Lysine Deacetylases 86 4.4 Proteins Containing Structural Zn 88 4.4.1 Zn Finger Proteins 88 Specificity Protein 1 89 Snail Homolog 1 89 Glioma-Associated Oncogene 90 4.4.2 p53 90 4.5 Summary 92 References 92 Chapter 5: Arsenic Carcinogenesis 104 5.1 Introduction 104 5.2 Cancer Epidemiology 105 5.2.1 Skin Cancers 105 5.2.2 Lung Cancer 106 5.2.3 Urinary Bladder and Kidney Cancer 107 5.2.4 Liver and Prostate Cancers 107 5.3 Arsenic Carcinogenesis in Laboratory Animals 107 5.4 Cell Proliferation/Stem Cells 108 5.5 DNA Repair/Co-mutagenesis 108 5.6 Aneuploidy/Clastogenesis 110 5.7 Epigenetics 110 5.7.1 DNA Methylation 110 5.7.2 Histone Modification 112 5.7.3 miRNA 113 5.8 Conclusions 113 References 114 Chapter 6: Cadmium Carcinogenesis and Mechanistic Insights 121 6.1 Introduction 123 6.2 Lung Cancer 125 6.2.1 DNA Repair 125 6.2.2 Apoptosis/Autophagy 126 6.2.3 EGF Receptor (EGFR) and Cell Cycle Regulatory Genes in Cadmium-Induced Lung Cancers 126 6.3 Renal Cancer 127 6.3.1 Cadmium Uptake by Kidneys 127 6.3.2 Apoptosis, Necrosis, and Autophagy in Proximal Tubule Epithelial Cells 128 6.3.3 Cell Survival Response 128 6.3.4 Notch1, Wnt/β-Catenin, and E-Cadherin-Mediated Cell Signaling in Cadmium-Exposed Renal Proximal Cells and Carcinogenesis 128 6.4 Prostate Cancer 129 6.4.1 Cell Transformation Studies 130 6.5 Breast Cancer 131 6.5.1 Estrogen and Estrogen Receptor 132 6.5.2 E-Cadherin, β-Catenin, and Associated Signaling Events 134 6.6 Pancreatic Cancer 135 6.7 General Molecular Pathways of Cadmium-Mediated Carcinogenesis 135 6.7.1 Oxidative Stress 136 6.7.2 DNA Damage Repair Pathways 136 6.7.3 Aberrant Gene Expression, Transcription, and Translation 138 6.7.4 Transcriptional and Translational Alterations 138 6.7.5 Cell Proliferation and Cycle Regulation 139 6.7.6 Cadmium: Apoptosis and Autophagy in Carcinogenesis 139 6.7.7 Epigenetics 140 6.8 Conclusions and Perspectives 141 References 142 Chapter 7: Molecular Mechanisms of Chromium-Induced Carcinogenesis 151 7.1 Chromium: History, Production, and Uses 152 7.2 Cr Exposure and Evidence of Carcinogenesis 152 7.3 The Role of Physicochemical Properties in Cr-Induced Carcinogenesis 153 7.4 Characteristics of Cr-Induced Lung Tumors 154 7.5 Potential Mechanisms of Cr(VI)-Induced Carcinogenesis 156 7.5.1 Multistage Carcinogenesis 157 7.5.2 Genomic Instability 160 7.5.3 Epigenetic Modification 174 7.6 Mechanism of Cr(VI)-Induced Carcinogenesis 180 References 182 Chapter 8: Mechanisms of Nickel Carcinogenesis 189 8.1 Introduction to Nickel 190 8.2 Overview of Cancer 191 8.3 Modes of Carcinogenesis 191 8.4 Environmental Exposure 192 8.5 Epidemiological Investigations 194 8.6 Animal Bioassays 194 8.7 In Vitro Investigations 195 8.8 Genetic Mechanisms Underlying Nickel Carcinogenesis 196 8.9 Epigenetic Mechanisms 196 8.9.1 Acetylation 198 8.9.2 MicroRNA 199 8.10 Conclusion 200 References 200 Chapter 9: Application of Metallomics and Metalloproteomics for Understanding the Molecular Mechanisms of Action of Metal-­Based Drugs 206 9.1 Introduction 208 9.2 Metallomics and Metalloproteomics: The Role in Metallodrug Research 210 9.2.1 Definition and Research Subjects in Metallomics 210 9.2.2 Metalloproteomics 211 9.3 The Technical Platform in Metallomics and Metalloproteomics 211 9.3.1 Chemical Speciation of Bioactive Metallome 212 9.3.2 Metalloproteome Separation and Identification 212 9.4 Biotransformation, Cellular Distribution, and Molecular Targets of Pt-and Ru-Based Anticancer Drugs/Agents 214 9.4.1 Platinum 214 9.4.2 Ruthenium 217 9.5 Multi-targeted Bi-Based Antimicrobial Drugs 219 9.6 Cytotoxicity of Metallic Nanoparticles 221 9.7 Conclusion and Perspective 224 References 225 Index 230 Front Matter....Pages i-xii Calcium Channels and Pumps: Importance During Lactation as Potential Targets for Breast Cancer....Pages 1-17 Tumor Development Through the Mg2+nifying Glass....Pages 19-38 Selenium: Roles in Cancer Prevention and Therapies....Pages 39-68 Zinc and Zinc-Dependent Proteins in Cancer and Chemotherapeutics....Pages 69-94 Arsenic Carcinogenesis....Pages 95-111 Cadmium Carcinogenesis and Mechanistic Insights....Pages 113-142 Molecular Mechanisms of Chromium-Induced Carcinogenesis....Pages 143-180 Mechanisms of Nickel Carcinogenesis....Pages 181-197 Application of Metallomics and Metalloproteomics for Understanding the Molecular Mechanisms of Action of Metal-Based Drugs....Pages 199-222 Back Matter....Pages 223-228