Cancer Letters

Cancer Letters

Volume 342, Issue 2, 28 January 2014, Pages 275-284
Cancer Letters

Mini-review
The epigenome and cancer prevention: A complex story of dietary supplementation

https://doi.org/10.1016/j.canlet.2012.01.021Get rights and content

Abstract

Epigenetic changes have been implicated in virtually all types of human malignancies. In contrast to genetic changes, epigenetic changes occur in a gradual manner during the tumorigenic process and they are potentially reversible. Because epigenetic changes have frequently been detected in high-risk populations, they are attractive targets to prevent the initiation of premalignant lesions or their advance to a malignant stage. A wide range of chemical entities has been found capable of altering the epigenome in animal models and humans. Epidemiological and laboratory-based studies suggested that these agents may have an anti-neoplastic effect against different cancer types. Several of these agents have been tested as dietary supplements, often with conflicting results. In this review, we discuss recent developments in our understanding of agents capable of modulating the epigenome and their potential to prevent human cancer when administered as dietary supplements.

Introduction

Epigenetics can be defined heritable changes in gene expression that occur without DNA sequence changes. It triggers initiation and/or maintaining of cell-type-specific transcriptional profiles and key role in cancer development. Three distinct mechanisms are well known to regulate the epigenome: DNA methylation, histone modifications, and small-interfering RNAs. Epigenetic processes by these mechanisms include genomic imprinting, gene silencing, X chromosome inactivation, reprogramming in transferred nuclei, and carcinogenesis [1], [2], [3], [4]. Epigenetic mechanisms are also believed to mediate gene-environment interactions and may serve as an interface between the genome and its environment [5]. Various environmental/lifestyle stressors and endogenous cues may induce alteration in the epigenome, thus deregulating different cellular process that may result in various disease including cancer.

Importantly, epigenetic changes in comparison with genetic ones are reversible and are acquired in a gradual manner. These distinguishing features make epigenetic changes attractive not only for cancer therapy but also for cancer prevention. Recent studies provide evidence that dietary factors including food supplementation may have an important impact on epigenetic states [6], [7], [8], underscoring the need for identifying epigenetic targets and critical window of vulnerability to environmental/dietary modulation, both of which may prove highly useful in the design of novels strategies for cancer control. The work on epigenetic mechanisms in regulation of cellular processes and epigenetic modifications in cancer cells induced by environmental factors have been recently reviewed [9], [10]. In this review, we will focus on recent evidence demonstrating the impact of dietary supplementation on epigenome and its potential cancer prevention.

Section snippets

DNA methylation

DNA methylation is an epigenetic mechanism that allows the regulation of transcription via the addition of methyl groups from S-adenosyl-l-methionine to the 5-carbon (C5) of the nucleotide cytosine. In general, DNA methylation in gene promoter regions results in gene silencing likely because of steric inhibition of transcription complexes binding to regulatory DNA. This reaction is catalyzed by DNA methyltransferases (Dnmt): Dnmt1, Dnmt2, Dnmt3a, Dnmt3b, and DnmtL. For example, Dnmt1 is thought

Acknowledgments

We apologize to authors whose relevant publications were not cited due to space limitation. The work in the Epigenetics Group at the International Agency for Research on Cancer (Lyon, France) is supported by grants from Institut National du Cancer (INCA, France), l’Agence Nationale de Recherche Contre le Sida et Hépatites Virales (ANRS, France), l’Association pour la Recherche sur le Cancer (ARC), France; and la Ligue Nationale (Française) Contre le Cancer, France (to Z.H.). The founders had no

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