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Cancer Sensitizing Agents for Chemotherapy: Role of Nutraceuticals in Cancer Chemosensitization

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Contents

Contributors

About the Editors

About the Series Editor

Aims and Scope for Series “Cancer Sensitizing Agents for Chemotherapy”

Preface

Chapter 1: Pathways Linked to Cancer Chemoresistance and Their Targeting by Nutraceuticals

Introduction

Chemotherapy

Alkylating Agents

Cell Cycle Inhibitors/Antimicrotubule Agents

Antimetabolites

Antibiotics

Topoisomerase Inhibitors

Targeted Therapy

Target-Specific Antibodies

Small Molecule Inhibitors

Chemoresistance: Problem in Curing Cancer

Mechanism of Chemoresistance

Drug Transporters

Enhanced DNA Repair System

Drug Inactivation

Altered Drug Targets

Epithelial-Mesenchymal Transition

Inhibition of Apoptosis

Autophagy

Aberrant Expression and Constitutive Activation of Transcription Factors

Nuclear Factor-Kappa B (NF-κB)

Signal Transducers and Activators of Transcription 3 (STAT-3)

Activating Protein-1 (AP-1)

Activation of Self-Renewal Pathways

Chemosensitization: An Approach to Target Cancer

Nutraceuticals as Chemosensitizers: Opportunities and Challenges

Conclusion

Conflict of Interest

Acknowledgments

References

Chapter 2: The Potential of Curcumin: A Multitargeting Agent in Cancer Cell Chemosensitization

Introduction

Molecular Targets of Curcumin

Chemosensitization Studies of Curcumin in Different Cancers

Curcumin Mediated Chemosensitization in Bladder Cancer

Curcumin Mediated Chemosensitization in Brain Cancer

Curcumin Mediated Chemosensitization in Breast Cancer

Curcumin Mediated Chemosensitization in Cervical Cancer

Curcumin Mediated Chemosensitization in Colon Cancer

Curcumin Mediated Chemosensitization in Esophageal Cancer

Curcumin Mediated Chemosensitization in Leukemia

Curcumin Mediated Chemosensitization in Lung Cancer

Curcumin Mediated Chemosensitization in Multiple Myeloma

Curcumin Mediated Chemosensitization in Ovarian Cancer

Curcumin Mediated Chemosensitization in Pancreatic Cancer

Curcumin Mediated Chemosensitization in Prostate Cancer

Curcumin Mediated Chemosensitization in Other Cancers

Hybrid Curcumin

Conclusion

Conflict of Interest

Acknowledgment

References

Further Reading

Chapter 3: Role of Resveratrol in Chemosensitization of Cancer

Introduction

Source and Chemistry of Resveratrol

Possible Molecular Mechanisms of Chemoresistance in Cancer

ATP-Dependent Drug Efflux

Drug Detoxification

Alterations in Drug Target Molecules

Alterations in DNA Damage Repair Pathways

Regulation of Cell Cycle Arrest

Regulation of Apoptosis

Deregulated Autophagy

Role of Cancer Stem Cells

Epigenetics and Chemoresistance

NF-κB Pathways

STAT3 Signaling

Ubiquitin-Proteasome System in Chemoresistance

Chemosensitization Studies Using Resveratrol in Vitro

Chemosensitization Studies Using Resveratrol in Vivo

Human Clinical Trials Involving Resveratrol in Cancer

Conclusion and Future Perspective

References

Further Reading

Chapter 4: Role of Tocotrienols in Chemosensitization of Cancer

Introduction

Source and Chemistry of Tocotrienols

Molecular Targets of Tocotrienols in Cancer

Mechanisms of Anticancer Action of Tocotrienols

Chemosensitization by Tocotrienols

Chemosensitization In Vitro

Gemcitabine

Capecitabine

Tamoxifen

Celecoxib

Paclitaxel/Docetaxel

Cisplatin

Doxorubicin/Epirubicin

EGFR Tyrosine Kinase Inhibitors

Met Inhibitor

Thalidomide/Bortezomib

TRAIL

Statins

Autophagy Inducers

Chemosensitization In Vivo

Gemcitabine

Capecitabine

Doxorubicin/Epirubicin

Statins

Chemosensitization in Human

Tamoxifen

Paclitaxel/Docetaxel/Epirubicin

Conclusion

References

Chapter 5: Chemosensitization by Ursolic Acid: A New Avenue for Cancer Therapy

Introduction

Chemosensitization of Cancer Cells

In vitro studies

In vivo studies

Safety and Efficacy

Conclusion and Future Direction

Acknowledgment

References

Chapter 6: Role of Fisetin in Chemosensitization

Introduction

Chemistry and Sources of Fisetin

Health Benefits of Flavonoids

Chemistry of Fisetin

Sources of Fisetin

Molecular Targets of Fisetin

Cell Growth and Proliferation

Cell Cycle

Apoptosis

Autophagy

Endoplasmic Reticulum Stress

Angiogenesis

Invasion and Metastasis

Epithelial-Mesenchymal Transition Markers

Others

Chemosensitization by Fisetin

Chemosensitization In Vitro

Chemosensitization in Animal Studies

Conclusion

Conflict of interest

References

Chapter 7: Role of Celastrol in Chemosensitization of Cancer

Introduction

Biological Source of Celastrol and Its Chemistry

Molecular Targets of Celastrol and Its Potential Mechanism(s) of Action

Anticancer and Chemosensitizing Effects of Celastrol

Conclusions

Conflict of Interest

Acknowledgments

References

Chapter 8: Role of Gambogic Acid in Chemosensitization of Cancer

Introduction

Source and Chemistry of GA

Molecular Targets of GA

Cell Proliferation

GA Inhibits Expression of COX-2

GA Inhibits Tubulin

Survival Pathways

Bcl-2 Family Proteins

Tumor Necrosis Factor-α (TNF-α)

NF-κB Signaling

Phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/AKT)

Mitogen-Activated Protein Kinase (MAPK)

Apoptosis

Metastasis

Chemokine X- Receptor 4 (CXCR4) and Downstream Signaling Pathways

Focal Adhesion Kinase (FAK)

Angiogenesis

GA Inhibits the Synthesis of Nitric Oxide

Chemo-Sensitization by GA

GA and Chemo-Sensitization In Vitro

GA and Chemo-Sensitization in Animal Studies

GA and Chemo-Sensitization in Human

Conclusion

References

Chapter 9: Role of Catechins in Chemosensitization

Introduction

Sources of Catechins

Structure and Chemistry of Catechins

Metabolism of Catechins

Proanthocyanidin (PAs, an Oligomer of Catechin and Epicatechin) Digestion in Vivo

Small Intestine and Colonic Catabolism of Catechins

Molecular Targets of the Catechin

Chemosensitization by Catechins

Chemosensitization in Vitro

Catechins and Curcumin

Catechins and Doxorubicin (DOX)

Catechins and Cisplatin

Catechins and RRx-001

Epigenetic Regulation by Catechins

Catechin and Dextran

Chemosensitization of Catechins Using Nanoparticles

Chemosensitization by EGCG and DOX-Loaded Polyion Complex (PIC) Micelle

Chemosensitization by TF/EGCG and Cisplatin-Loaded Poly-(Lactide-co-Glycolide) NPs

Chemosensitization in Vivo

Catechins and Atorvastatin

Catechin and Cisplatin

Catechin and Dextran

Catechins in Oral and Gastrointestinal Cancer

Human Trials

Prostate Cancer

Breast Cancer

Colorectal Cancer

Implication of Catechins in Other Diseases

Catechins in Lung Diseases

EGCG in Obesity and Diabetes

EGCG in Neurodegenerative Diseases

EGCG in the Cardiovascular Disease (CVD)

Conclusion

Conflict of Interest

Acknowledgment

References

Further Reading

Chapter 10: Anticancer Attributes of Silibinin: Chemo- and Radiosensitization of Cancer

Introduction

Structural Composition and Bioavailability of Silymarin/Silibinin

Targeting of Various Attributes of Cancer Growth and Progression

Inhibition of Growth of Various Types of Cancer Cells

Alteration of Cell Cycle Progression and Related Proteins

Silibinin Suppresses Mitogenic and Survival Pathways

Angioprevention by Silibinin

Silibinin Targets Epithelial-Mesenchymal Transition and Metastasis

Silibinin Targets the Tumor Microenvironment and Cancer Stem Cells

Silibinin as Chemosensitizer for Cancer Cells

Silibinin and Paclitaxel

Silibinin and HDAC or DNMT Inhibitors

Silibinin and Tyrosine Kinase Inhibitor

Silibinin and Mitoxantrone or Docetaxel

Silibinin and Arsenic Trioxide

Silibinin and Cisplatin or Carboplatin

Silibinin and Doxorubicin

Silibinin as Radiosensitizer for Cancer Cells

Conclusions

References

Chapter 11: Berberine as an Adjuvant and Sensitizer to Current Chemotherapy

Introduction

Source and Chemistry

Evidence Showing the Potential of Berberine as a Chemosensitizer

5-Fluorouracil

Arsenic Trioxide

BCNU

Camptothecin

Cetuximab, Erlotinib, Gefitinib and Lapatinib

Cisplatin

Doxorubicin

Gemcitabine

Paclitaxel

Tamoxifen

TRAIL

Hormetic Effects of Berberine in In Vitro Studies

Chemosensitization In Vivo and Other Beneficial Properties

Berberine in Human Trials

Conclusion

Conflict of Interest

Acknowledgments

References

Chapter 12: Role of Emodin in Chemosensitization of Cancer

Introduction

Anti-cancer Activities of Emodin

Anti-cancer Activities of Emodin Analogues

Chemosensitization of Tumors by Emodin

Conclusions

Acknowledgments

References

Chapter 13: Role of Piperine in Chemoresistance

Introduction

Sources and Chemistry of Piperine

Piperine Extraction and Quantification

Medicinal & Pharmacological Activities of Piperine

Anti-microbial Activity

Effects on the Gastrointestinal System

Analgesic, Anticonvulsant and Antidepressant Effects

Antiasthmatic Activity

Anti-thyroid Activity

Antidiabetic Activity

Hepatoprotective Effect

Immuno-Modulatory Activity

Mechanism of Action of Piperine

Cell Cycle

Apoptosis

Cell Survival

Role of PI3K-Akt-mTOR signaling in cell survival

Autophagy

Angiogenesis

Invasion and Metastasis

Piperine and Oxidative Stress

Inflammation

Piperine as a Bioenhancer

Chemoresistance and Chemosensitisation

Drug Metabolism

Drug Transporters

Interactions of Piperine With Chemotherapeutic Drugs

M Phase-Dependent Chemotherapeutic Drugs

Piperine and Docetaxel

Piperine and Paclitaxel

Piperine and Etoposide

Piperine and Vinblastine

S Phase-Dependent Chemotherapeutic Drugs

Piperine and Doxorubicin

Piperine and 5- FU

G2 Phase-Dependent Chemotherapeutic Drugs

Mitoxantrone

Cisplatin

Conclusion

References

Further Reading

Chapter 14: Role of Deguelin in Chemoresistance

Introduction

Source and Chemistry of Deguelin

Molecular Targets of Deguelin

Chemosensitization by Deguelin

Conclusion

Acknowledgements

References

Chapter 15: Garcinol: Preclinical Perspective Underpinning Chemo- and Radiosensitization of Cancer

Introduction

Garcinol Bioavailability

Garcinol: Therapeutic Targets

Anti-Inflammatory Effect of Garcinol

Cyclooxygenase-2

Lipoxygenase

Inducible Nitric Oxide Synthase (iNOS)

Garcinol and Anti-Oxidant Activity

Garcinol and Apoptosis

Garcinol and Cell Cycle

Garcinol and Chromatin Modification

Histone Acetyltransferase Inhibition

Garcinol and microRNA

Garcinol and Cell Signaling

Garcinol and NF-κB Signaling

Garcinol and STAT Signaling

Garcinol and Akt Signaling

Garcinol and Wnt Signaling

Garcinol and MAP Kinase Signaling

Garcinol, Cancer Stem Cells and ABCG2

Garcinol: Invasion and Metastasis

Garcinol and Angiogenesis

Systemic Anticancer and Chemo-Sensitizing Effects of Garcinol

Garcinol and Head and Neck Cancer

Garcinol and Lung Cancer

Garcinol and Breast Cancer

Garcinol and Hepatocellular Carcinoma

Garcinol and Pancreatic Cancer

Garcinol and Colon Cancer

Garcinol and Prostate Cancer

Garcinol and Haematological Malignancies

Garcinol and TRAIL Sensitization

Garcinol and Radiosensitization

Garcinol Combination With Other Natural Agents on Cancer Therapy

Conclusion

References

Chapter 16: Chemopreventive and Anticancer Effects of Plumbagin: Novel Mechanism(s) via Modulation of Cellular Redox

Introduction

Occurrence and Isolation of Plumbagin

Antioxidant Properties of Plumbagin

Chemopreventive and Antitumor Properties of Plumbagin

Leukemia

Lung Cancer

Breast Cancer

Prostate and Colon Cancer

Cervical Cancer

Liver Cancer

Melanoma

Myeloma

Ovarian Cancer

Pancreatic Cancer

Osteosarcoma

Antiangiogenic Property of Plumbagin

Plumbagin Nano-Particle Preparations

Anti-inflammatory Properties of Plumbagin

Chemosensitizing Properties of Plumbagin

Conclusion

References

Chapter 17: Role of Zerumbone in the Chemosensitization of Cancer Cells

Introduction

Source and Chemistry of Zerumbone

Zerumbome Promotes the Chemosensitization of Paclitaxel and Cisplatin in Cancer Cells

Zerumbone is a Dual Inhibitor of JAK/STAT3 and NF-κB Signaling

Zerumbone-Mediated Chemosensitization In Vitro and In Vivo

Conclusion

References

Chapter 18: Multitalented Ginger and Its Clinical Development for Cancer Treatment

Introduction

Almighty Ginger to Treat Mighty Cancer

Multitargeted Anticancer Properties

Overcome Chemosensitization of Cancer

Combat Side Effects of Chemotherapy

Clinical Translation of Ginger: Major Roadblocks

Innovative Modern Concepts to Further Clinical Translation of Ginger

Network Pharmacology

Reverse Pharmacokinetics

PK-PD Modeling

Conclusion

Conflict of Interest

References

Index

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