Epigenetics of Cancer Prevention

Anupam Bishayee,Deepak Bhatia

• Publisher: Academic Press
• Year: 2018
• ISBN:
  9780128125663
• Topic: Medicina
• Subtopic: Biotecnología en medicina

Epigenetics of Cancer Prevention, Volume Ten is the first to look at epigenetics and chemoprevention together. Although there is numerous scientific data available on how epigenetics can lead to cancer and how chemoprevention can be beneficial in the treatment of, or improvement of quality of life, together they will set an advanced understanding for the reader in this upcoming field of chemoprevention influencing epigenetics. This book discusses molecular epigenetic targets of natural products, such as green tea polyphenols, curcumin and resveratrol, and organ specific epigenetic targets related to diverse types of cancer, for example prostate, colorectal, breast, lung and skin cancers.

Additionally, it encompasses a discussion on research methods and limitations to study epigenetics and epigenomics of chemopreventive drugs and personalized cancer treatment with phytochemicals. The book is ideal for cancer researchers, health care professionals and all individuals who are interested in cancer prevention research and its clinical applications, especially in natural remedies.

• Lists natural agents, including nutraceuticals, and their effects on normal or tumor genome
• Addresses various epigenetic systems and mechanisms in the regulation and support of the mammalian genome
• Discusses how various parts of dietary phytochemicals can influence or modify epigenetic mechanisms in several types of cancer

Part I

Molecular Epigenetic Targets of Natural Products

Outline

1. Chapter 1. Genetic and Epigenetic Targets of Natural Dietary Compounds as Anticancer Agents
2. Chapter 2. Epigenetic Dietary Interventions for Prevention of Cancer
3. Chapter 3. Natural Anticancer Agents: Modifying the Epigenome to Prevent and Treat Cancer
4. Chapter 4. Histone Deacetylase Inhibitors in Cancer Prevention and Therapy
5. Chapter 5. Epigenetic Effects of Curcumin in Cancer Prevention
6. Chapter 6. The Epigenetic Targets of Berry Anthocyanins in Cancer Prevention
7. Chapter 7. Isothiocyanates, Epigenetics, and Cancer Prevention
8. Chapter 8. Epigenetic Mechanisms of Resveratrol and Its Analogs in Cancer Prevention and Treatment
9. Chapter 9. Epigenetic Mechanisms of Quercetin and Other Flavonoids in Cancer Therapy and Prevention

Chapter 1

Genetic and Epigenetic Targets of Natural Dietary Compounds as Anticancer Agents

Qiwen Shi^1,2, Anupam Bishayee³, and Deepak Bhatia^{4 1}Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Hangzhou, China ²Zhejiang University of Technology, Hangzhou, China ³Lake Erie College of Osteopathic Medicine, Bradenton, FL, United States ⁴Department of Pharmacogenomics, Bernard J Dunn School of Pharmacy, Shenandoah University, Fairfax, VA, United States

Abstract

Cancer is a heterogenous disease characterized by changes in the expression of multiple genes caused by genetic alternations and epigenetic modifications. Studies of the changes in genetic pathways and epigenetic regulation in tumor development and progression have provided a large pool of potential targets for anticancer therapy. In recent decades, numerous natural dietary products, such as curcumin, theanine, luteolin and epigallocatechin-3-gallate, have been identified as anticancer lead molecules with the ability to affect gene expression through both genetic and epigenetic mechanisms and have attracted considerable attentions in cancer treatment and prevention. This chapter focuses on the main genetic and epigenetic targets of anticancer dietary molecules, covering three of the most common genetic mutations (i.e. mutations in epidermal growth factor receptor, p53 and K-Ras) in cancer patients and epigenetic targets, such as DNA methyltransferases, histone deacetylases, histone acetyltransferases and changes in noncoding RNA expression. It summarizes miRNA dysregulation according to cancer type as well as the epigenetic targets of 11 common natural dietary compounds. The potential and current limitations of bioactive dietary molecules for the transition from laboratory to clinic in cancer management are also discussed.

Keywords

Cancer; Epigenetic signaling; Genetic targets; DNA methyltransferases; Histone acetyltransferases; Histone deacetylases; miRNA; Natural dietary compounds

Introduction

Cancer, a leading cause of death worldwide with an increasing incidence and mortality, remains a major public health problem in our society. It is widely accepted that cancer is a heterogeneous group of disorders driven by both genetic lesions and epigenetic plasticity. Acquired genetic mutations are the primary cause of cancer initiation and progression, while microenvironment-mediated epigenetic perturbations play a vital role in neoplastic development.

Natural dietary compounds have received tremendous attention for their efficacy in cancer chemoprevention due to the demonstration, from epidemiological studies, of an association between consumption of fruits and vegetables and the reduced risk of various cancers. In past decades, accumulated evidence has shown that natural active compounds in the diet can exhibit anticancer properties through multiple mechanisms, including modifying epigenetic patterns of oncogenes and tumor suppressor genes, targeting molecules and signaling pathways associated with tumor development, optimizing immune responses and tumor microenvironments, and reversing of drug resistance (Huang et al., 2016).

As a consequence of evolution, natural origin molecules are often complex and may affect more than one target. This chapter discusses different mechanisms of genetics changes and epigenetic modifications in cancer and describes the main genetic and epigenetic modifications targeted by natural dietary compounds in cancer prevention and treatment.

Genetic Mutations in Cancer Targeted by Natural Dietary Products

Aberrant gene expression due to specific activating mutations in oncogenes and prometastatic genes, or silencing mutations in tumor suppressor genes, is believed to be the driver of cancer initiation and progression. A certain proportion of mutations are inherited, while the majority of mutations are considered to be the result of accumulated changes in response to endogenous factors and environmental factors throughout one's life. The identification and verification of these so-called “driver mutations” have provided a pool of promising drug targets for which cancer treatment could achieve considerable progress. Table 1.1 lists the important genetic mutations in lung, breast, and colorectal cancers as well as acute myeloid leukemia, and the following subsections cover three common genetic mutations targeted by dietary compounds.

Epidermal Growth Factor Receptor

The epidermal growth factor receptor (EGFR) is a class of membrane receptor tyrosine kinase that is frequently amplified and overexpressed in a variety of tumors. Genetic aberration in EGFR has been validated as a key driver in the progression and malignancy of various cancers. Currently, the Food and Drug Administration has approved a dozen small-molecule tyrosine kinase inhibitors (TKIs). Although these inhibitors have exhibited excellent potency and strong efficacy, new resistance and a narrow therapeutic index have been realized...