Epigenetic targets of bioactive dietary components for cancer prevention and therapy

Abstract

The emergent interest in cancer epigenetics stems from the fact that epigenetic modifications are implicated in virtually every step of tumorigenesis. More interestingly, epigenetic changes are reversible heritable changes that are not due to the alteration in DNA sequence but have potential to alter gene expression. Dietary agents consist of many bioactive ingredients which actively regulate various molecular targets involved in tumorigenesis. We present evidence that numerous bioactive dietary components can interfere with various epigenetic targets in cancer prevention and therapy. These agents include curcumin (turmeric), genistein (soybean), tea polyphenols (green tea), resveratrol (grapes), and sulforaphane (cruciferous vegetables). These bioactive components alter the DNA methylation and histone modifications required for gene activation or silencing in cancer prevention and therapy. Bioactive components mediate epigenetic modifications associated with the induction of tumor suppressor genes such as p21(WAF1/CIP1) and inhibition of tumor promoting genes such as the human telomerase reverse transcriptase during tumorigenesis processes. Here, we present considerable evidence that bioactive components and their epigenetic targets are associated with cancer prevention and therapy which should facilitate novel drug discovery and development. In addition, remarkable advances in our understanding of basic epigenetic mechanisms as well as the rapid progress that is being made in developing powerful new technologies, such as those for sensitive and quantitative detection of epigenetic and epigenomic changes in cancer biology, hold great promise for novel epigenetic approaches to cancer prevention and therapy.

Fig. 1

Schematic diagram illustrating DNA methylation catalyzed by DNMTs. a The DNA methylation process is catalyzed by the DNMTs by adding a methyl group (CH₃) from SAM to the 5-position of the cytosine ring. SAM donates a methyl group and is then converted into SAH. b Methylated cytosine moieties in CpG dinucleotides within a gene promoter. c DNMTs convert unmethylated DNA into methylated DNA in chromatin. White circles unmethylated CpG sites, green circles hypermethylated CpG sites, yellow circles histone proteins, red thread DNA

Fig. 2

Schematic representation of histone modifications. HATs induce relaxed chromatin which allows access to the various transcriptional factors associated with gene activation. HDACs induce closed chromatin associated with gene activation. Various bioactive compounds such as EGCG, sulforaphane, and curcumin are linked with alterations of both HATs and HDACs. Yellow circle histone protein, red thread DNA; AC acetylation, TF transcription factor