Natural products modulating epigenetic mechanisms by affecting histone methylation/demethylation: Targeting cancer cells

Abstract

Many natural products can exert anticancer or chemopreventive activity by interfering with the cellular epigenetic machinery. Many studies indicate the relevance of affecting DNA methylation and histone acetylation, however the influence on the mechanisms related to histone methylation are often overlooked. This may be associated with the lagging evidence that changes in the action of histone methylation writers and erasers, and subsequent alterations in the profile of histone methylation are causally related with carcinogenesis. Recent animal studies have shown that targeting histone methylation/demethylation affects the course of experimentally induced carcinogenesis. Existing data suggest that numerous natural compounds from different chemical groups, including green tea polyphenols and other flavonoids, curcuminoids, stilbene derivatives, phenolic acids, isothiocyanates, alkaloids and terpenes, can affect the expression and activity of crucial enzymes involved in the methylation and demethylation of histone lysine and arginine residues. These activities have been associated with the modulation of cancer‐related gene expression and functional changes, including reduced cell proliferation and migration, and enhanced apoptosis in various cancer models. Most studies focused on the modulation of the expression and/or activity of two proteins ‐ EZH2 (a H3K27 methyltransferase) and LSD1 (lysine demethylase 1A ‐ a H3K4/9 demethylase), or the effects on the global levels of histone methylation caused by the phytochemicals, but data regarding other histone methyltransferases or demethylases are scarce. While the field remains relatively unexplored, this review aims to explore the impact of natural products on the enzymes related to histone methylation/demethylation, showing their relevance to carcinogenesis and cancer progression.

Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases—Focus on Epigenetic Mechanisms

“…Due to the relatively small number of studies exploring the epigenetic mechanisms of EGCG in gynecological cancers, we can rely on the published results regarding other types of cancer, where EGCG affects multiple molecular targets involved in cancer initiation, promotion, and progression. A good example that links epigenetic aberration to tumor development is reviewed by Dorna et al [ 264 ]. The pro-apoptotic or antiproliferative effects of EGCG resulting from changes in gene expression observed in in vitro studies are most likely related to a modification of the action of methylation enzymes such as DNMTs and a modification of histone proteins.…”

Exploring anticancer properties of the phytoconstituents and comparative analysis of their chemical space parameters with USFDA‐approved synthetic anticancer agents

“…Natural products invoved in gene expression by epigenetic modifications. Compounds such as epigallocatechin gallate (EGCG) and sulforaphane obtained from cruciferous vegetables can regulate DNA methylation and acetylation and affect gene transcription (Dorna et al, 2023).…”