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Selenium and Selenoproteins in Cancer

Copyright

Contents

Contributors

Preface

Chapter One: The Epidemiology of Selenium and Human Cancer

1. Introduction

2. Selenium and Cancer: Scope of Research

3. Observational Studies

4. Randomized Controlled Trials

5. The Nutritional Prevention of Cancer Trial

6. The Selenium and Vitamin E Cancer Prevention Trial

7. The Other Trials

8. A Natural Experiment on Selenium and Cancer

9. Selenium in Cancer Therapy

10. Conclusion

Acknowledgments

References

Chapter Two: Selenoproteins in Tumorigenesis and Cancer Progression

1. Introduction

2. Selenoprotein Production

3. Investigating Selenoproteins Through Sec tRNA Mutations

4. Role of Specific Selenoproteins in Tumorigenesis

4.1. Selenoprotein P

4.2. Glutathione Peroxidases

4.3. Thioredoxin Reductases

4.4. Selenoprotein F

5. Considerations and Conclusions

Acknowledgments

References

Chapter Three: Selenoproteins and Metastasis

1. Introduction

2. Metastasis

2.1. Local Invasion

2.2. Intravasation

2.3. Survival in Vasculature, Extravasation, and Formation of Micrometastases

3. Dietary Selenium and Selenium Supplementation

4. Thioredoxin Reductases and Redox Tone

5. GPX and ROS Regulation

6. Selenoproteins Involved in ER Stress and Calcium Flux

7. Other Potential Roles for Selenoproteins in Metastasis

8. Conclusions

Acknowledgments

References

Chapter Four: Selenium-Dependent Glutathione Peroxidases During Tumor Development

1. Introduction

2. Expression Profile of Se-Dependent GPxes in Different Types of Tumors

3. Hydroperoxides and Redox Signaling During Cancer Development

4. Impact of Individual GPxes on Tumor Development

4.1. GPx1

4.1.1. Cell Death

4.1.2. Redox Signaling

4.1.3. Metabolism

4.2. GPx2

4.2.1. Cell Death

4.2.2. Redox Signaling

4.3. GPx3

4.3.1. Cell Death

4.3.2. Redox Signaling

4.4. GPx4

4.4.1. Cell Death

4.4.2. Redox Signaling

5. Conclusions

Acknowledgment

References

Chapter Five: Targeting the Selenoprotein Thioredoxin Reductase 1 for Anticancer Therapy

1. Introduction

1.1. The Thioredoxin System

1.2. Thioredoxin Reductase 1

2. TrxR1 as an Important Enzyme in Cancer

3. Conclusions

Acknowledgments

References

Chapter Six: The Regulation of Pathways of Inflammation and Resolution in Immune Cells and Cancer Stem Cells by Selenium

1. Tumor Microenvironment: Interplay With Immune Cells and Pathways of Inflammation

2. Selenium-Dependent Effects on Cancer Stem Cells in Leukemia

3. Interaction of LSCs With Immune Cells Mediated by CyPGs

4. Targeting LSC Metabolism With Selenium

5. Summary

Acknowledgments

References

Chapter Seven: Selenium and Breast Cancer Risk: Focus on Cellular and Molecular Mechanisms

1. Breast Cancer: General Aspects

2. Se: Nutritional Aspects

3. Se and Breast Cancer

3.1. Evidence From Human Studies

3.2. Evidence From Animal Models

3.2.1. Se Chemopreventive Effects

3.2.2. Se Chemotherapy Effects

4. Cellular and Molecular Mechanisms of Se in Breast Cancer Prevention and Treatment

4.1. Chemoprotection

4.2. Chemoprevention

4.3. Chemotherapy

4.4. Emerging Mechanisms

4.4.1. Polymorphisms in Genes Coding Selenoproteins

4.4.2. New Functions of Selenoproteins

4.4.3. Epigenetic Mechanisms

4.4.4. Long-Term Influence of Early-Life Se Exposure on Later Breast Cancer Risk

5. Se Toxic and Procarcinogenic Effects in Breast Cancer

6. Concluding Remarks and Future Perspectives

Acknowledgments

References

Chapter Eight: Selenium and Epigenetics in Cancer: Focus on DNA Methylation

1. Introduction

2. Selenium and DNA Methylation

2.1. Selenium, DNA Methyltransferase, and Global DNA Methylation

2.2. Selenium and Methylation of Tumor Suppressor Genes

2.3. Possible Mechanisms Underlying Se-Induced DNA Hypomethylation Under Different Levels of Exposure/Intake

3. Methylation of Selenoprotein-Encoding Genes

3.1. Methylation Status in Human Cancer Tissues

3.2. Methylation Status in Human Cancer Cell Lines

4. Conclusions

Acknowledgments

References

Chapter Nine: Selenium and Cancer Stem Cells

1. Introduction

2. Selenium, Human Health, and Cancer

3. CSCs: A Debated Theory

4. Cellular Properties of CSCs: Focus on Redox Regulation

5. Selenium and CSCs

5.1. GPx-2 and Other Selenoproteins in CSC Biology

5.2. Targeting the Wnt/β-Catenin Pathway With Se Compounds

5.3. Se Compounds Modulate Arachidonic Acid Metabolism and PPAR-Gamma Activity in CSCs

6. Conclusions

Acknowledgments

Disclosure Statement

References

Chapter Ten: Selenocompounds in Cancer Therapy: An Overview

1. Introduction

2. Seleniumo-Containing Molecules in Cancer Therapy

2.1. Inorganic Selenium Species

2.2. Selenium-Containing Amino Acids

2.3. Methylseleninic Acid

2.4. Diselenides

2.5. Selenocyanates and Isoselenocyanates

2.6. Selenoureas

2.7. Selenocarbonyl Derivatives

2.8. Selenoxides

2.9. Selenazoles and Selenadiazoles

2.10. Isoselenazolones

3. Selenium Compounds Mechanism of Action in Tumor Cells

3.1. The Selective Uptake of Se in Cancer Cells

3.2. The Redox-Active Character of Organoselenium Compounds Relevant to Their Anticancer Properties

4. Cell Signaling Pathways Influenced by Se Compounds

4.1. PI3K/Akt and MAPK Pathways

4.2. ER Stress Response to Protein Misfolding

4.3. Angiogenesis and Cancer Progression

4.4. GSTP as Target of Se Organic Anticancer Agents

4.5. Epigenetics of Se Compounds

5. Conclusion

Acknowledgments

References

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