Plant phytochemicals as epigenetic modulators: role in cancer chemoprevention

Abstract

In recent years, "nutri-epigenetics," which focuses on the influence of dietary agents on epigenetic mechanism(s), has emerged as an exciting novel area in epigenetics research. Targeting of aberrant epigenetic modifications has gained considerable attention in cancer chemoprevention research because, unlike genetic changes, epigenetic alterations are reversible and occur during early carcinogenesis. Aberrant epigenetic mechanisms, such as promoter DNA methylation, histone modifications, and miRNA-mediated post-transcriptional alterations, can silence critical tumor suppressor genes, such as transcription factors, cell cycle regulators, nuclear receptors, signal transducers, and apoptosis-inducing and DNA repair gene products, and ultimately contribute to carcinogenesis. In an effort to identify and develop anticancer agents which cause minimal harm to normal cells while effectively killing cancer cells, a number of naturally occurring phytochemicals in food and medicinal plants have been investigated. This review highlights the potential role of plant-derived phytochemicals in targeting epigenetic alterations that occur during carcinogenesis, by modulating the activity or expression of DNA methyltransferases, histone modifying enzymes, and miRNAs. We present in detail the epigenetic mode of action of various phytochemicals and discuss their potential as safe and clinically useful chemopreventive strategies.

Fig. 1

Epigenetic pathways affected by plant phytochemicals. Numerous pathways are deregulated in cancer cells. Major epigenetic mechanisms that regulate gene expression are DNA methylation, alterations in the chromatin structure by post-translational modification of histones, and miRNAs which can either degrade mRNAs or modulate their translation process. Plant phytochemicals have shown to affect epigenetic pathways. demonstrates regulation; demonstrates inhibition