Dietary manipulation of histone structure and function.

The influence of epigenetic alterations during cancer has gained increasing attention over the recent years and has resulted in a paradigm shift in our understanding of mechanisms leading to cancer susceptibility. These features are potentially reversible and may affect genomic stability and expression of genes, including tumor suppressor genes and oncogenes. The reversible acetylation of histones is an important mechanism of gene regulation. Targeting the epigenome, including the use of histone deacetylase (HDAC) inhibitors, is a novel strategy for cancer chemoprevention. We have found that sulforaphane (SFN), a compound found in cruciferous vegetables, inhibits HDAC activity in human colorectal and prostate cancer cells. The ability of SFN to target aberrant acetylation patterns, in addition to effects on phase 2 enzymes, may make it an effective chemoprevention agent. Other dietary agents such as butyrate, allyl sulfides and organoselenium compounds have also shown promise as HDAC inhibitors. These studies are significant because of the potential to qualify or change recommendations for high-risk cancer patients, thereby increasing their survival through simple dietary choices, such as incorporating easily accessible foods into a patients diet. The work to date provides a scientific foundation for future large-scale human clinical intervention studies with dietary agents that affect the epigenome.

Overview