Dietary phytochemicals as epigenetic modifiers in cancer: Promise and challenges

Abstract

The influence of diet and environment on human health has been known since ages. Plant-derived natural bioactive compounds (phytochemicals) have acquired an important role in human diet as potent antioxidants and cancer chemopreventive agents. In past few decades, the role of epigenetic alterations such as DNA methylation, histone modifications and non-coding RNAs in the regulation of mammalian genome have been comprehensively addressed. Although the effects of dietary phytochemicals on gene expression and signaling pathways have been widely studied in cancer, the impact of these dietary compounds on mammalian epigenome is rapidly emerging. The present review outlines the role of different epigenetic mechanisms in the regulation and maintenance of mammalian genome and focuses on the role of dietary phytochemicals as epigenetic modifiers in cancer. Above all, the review focuses on summarizing the progress made thus far in cancer chemoprevention with dietary phytochemicals, the heightened interest and challenges in the future.

Introduction

The term ‘Epigenetics’ was coined by British developmental biologist Conrad Waddington, derived from the combination of word ‘epigenesis’ and ‘genetics’ [1]. Epigenetics is defined as the branch of biology which studies the casual interactions between genes and their products, where ‘Epi’ means above or over and ‘genetics’ reflects the involvement of genes and heredity. Today epigenetics may be defined as the study of chemical changes to the genome that are heritable and modulate gene expression or cellular phenotype through mechanisms involving how DNA is packaged and expressed without any alterations in the gene nucleotide sequence itself [1], [2]. Epigenetic mechanisms have been shown to be essential in regulating normal cellular functions and play important role during developmental stages. In mammals, DNA methylation is associated with several key processes such as genomic imprinting, X-chromosome inactivation and tissue-specific gene expression [3], [4], [5], [6]. Histone methylation and acetylation patterns were demonstrated to be closely associated with cognitive functions such as long term memory formation and storage [7], [8], [9]. Epigenetic alterations have been implicated in several pathologies such as cancer, metabolic syndrome, Alzheimer’s disease and other neurological disorders [10], [11], [12], [13]. Unlike genetic changes in the genome such as mutation, epigenetic modifications are potentially reversible and can be modified by environmental, dietary and lifestyle factors. Epigenetic mechanisms have been implicated in physiological responses to intrinsic and extrinsic environmental stimuli such as nutrition, radiation, exposure to chemicals, toxins and hormones [14], [15]. The epigenetic diet, or the control of epigenetic modifiers through consumption of dietary phytochemicals, is of extreme interest. Several studies suggest that dietary phytochemicals are not only an essential source of nutrients but also important in the elimination of cancer as a life-threatening disease [14], [15]. In this review, we focused on the role of dietary phytochemicals as epigenetic modifiers. We discussed in detail different mechanisms of epigenetic modifications in mammals and present a comprehensive overview of the current state of knowledge on dietary bioactive compounds and their influence on various epigenetic mechanisms highlighting their role as potential anticancer agents.