Dietary factors and epigenetic regulation for prostate cancer prevention

Abstract

The role of epigenetic alterations in various human chronic diseases has gained increasing attention and has resulted in a paradigm shift in our understanding of disease susceptibility. In the field of cancer research, e.g., genetic abnormalities/mutations historically were viewed as primary underlying causes; however, epigenetic mechanisms that alter gene expression without affecting DNA sequence are now recognized as being of equal or greater importance for oncogenesis. Methylation of DNA, modification of histones, and interfering microRNA (miRNA) collectively represent a cadre of epigenetic elements dysregulated in cancer. Targeting the epigenome with compounds that modulate DNA methylation, histone marks, and miRNA profiles represents an evolving strategy for cancer chemoprevention, and these approaches are starting to show promise in human clinical trials. Essential micronutrients such as folate, vitamin B-12, selenium, and zinc as well as the dietary phytochemicals sulforaphane, tea polyphenols, curcumin, and allyl sulfur compounds are among a growing list of agents that affect epigenetic events as novel mechanisms of chemoprevention. To illustrate these concepts, the current review highlights the interactions among nutrients, epigenetics, and prostate cancer susceptibility. In particular, we focus on epigenetic dysregulation and the impact of specific nutrients and food components on DNA methylation and histone modifications that can alter gene expression and influence prostate cancer progression.

Figure 1

Histone acetylation and DNA methylation: epigenetic mechanisms that affect gene expression. (A) Closed chromatin structure and transcriptional silencing. Hypoacetylation due to HDAC activity combined with localized promoter hypermethylation, regulated by DNMT. (B) Open chromatin structure and gene activation. Dietary compounds, such as SFN inhibit HDAC and DNMT, facilitating reexpression of silenced tumor suppressors in cancers, such as p21. Open chromatin is associated with increased acetylation of histone tails by HAT and the recruitment of transcription factors and their coactivator complexes. DNMT, DNA methyltransferase; HAT, histone acetyltransferase; HDAC, histone deacetylase; SFN, sulforaphane.

Figure 2

Overview of mechanisms by which diet and dietary factors influence DNA and histone methylation. DNA methylation is influenced by the methyl pool involving SAM, which acts as a substrate for DNMT that transfer one-carbon units to DNA. SAM also serves as donor for histone methylation. Dietary factors that can regulate DNA and histone methylation include the following: 1) vitamins: vitamin B-6, vitamin B-12, and riboflavin; 2) minerals: zinc and selenium; 3) phytochemicals: genistein, tea polyphenols, and isothiocyanates; and 4) other dietary factors: methionine and choline. BHMT, betaine-homocysteine methyltransferase; CBS, cystathionine β-synthase; COMT, catechol-O-methyltransferase; DHF, dihydrofolate; MS, methionine synthase; MTHFR, 5, 10-methylenetetrahydrofolate reductase; SAH, S-adenosyl homocysteine; SAM, S-adenosyl methionine; SHMT, serine hydroxymethyltransferase; THF, tetrahydrofolate.