Impact of Epigenetic Dietary Components on Cancer through Histone Modifications

Abstract

Epigenetics, the study of heritable changes in gene expression without modifying the nucleotide sequence, is among the most important topics in medicinal chemistry and cancer prevention and therapy. Among those changes, DNA methylation and histone modification have been shown to be associated with various types of cancers in a number of ways, many of which are regulated by dietary components that are mostly found in plants. Although mechanisms of nutrient components affecting histone acetylation/deacetylation in cancer are widely studied, how those natural compounds affect cancer through other histone modifications, such as methylation, phosphorylation and ubiquitylation, is rarely reviewed. Thus, this review article discusses impacts on histone acetylation as well as other histone modifications by nutrient components, such as genistein, resveratrol, curcumin, epigallocatechin-3-gallate (EGCG), 3,3'-diindolylmethane (DIM), diallyl disulfide, garcinol, procyanidin B3, quercetin, sulforaphane and other isothiocyanates that have been recently reported in vivo as well as in various types of cancer cell lines.

Figure 1

Chromatin conformational change affected by dietary components. Dietary components can affect gene expression by changing chromatin conformation through HAT and/or HDAC activities. HAT enhancers and HDAC inhibitors, such as diallyl disulfide, genistein and sulforaphane, trigger a loose chromatin which allows DNA accessibility to transcriptional factors, leading to gene expression. In contrast, HAT inhibitors, such as curcumin, EGCG and quercetin, cause a tight chromatin which makes DNA inaccessible to transcriptional factors, resulting in gene silencing. Green cylinder represents histone octamer. Red line represents DNA. Blue dot represents acetyl group.