OREGON STATE UNIVERSITY
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Emily Ho, PhDProfessor, Endowed Director of the Moore Family Center for Whole Grain Foods, Nutrition & Preventive Health |
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| Abstract: The classic view of cancer etiology is that genetic alterations damage DNA structure and induce mutations resulting in non-functional proteins that lead to disease progression. More recently, the role of epigenetic alterations during cancer has gained increasing attention. The reversible acetylation of histones is an important mechanism of gene regulation. During cancer progression, specific modifications in acetylation patterns on histones are apparent. Targeting the epigenome, including the use of histone deacetylase (HDAC) inhibitors, is a novel strategy for cancer chemoprevention. Recently, drugs classified as HDAC inhibitors, have shown promise in cancer clinical trials. Based on the similarity of sulforaphane (SFN) metabolites and other phytochemicals to known pharmacological HDAC inhibitors, we previously demonstrated that sulforaphane, a phytochemical derived from cruciferous vegetables, acts as an HDAC inhibitor in the prostate, causing enhanced histone acetylation, de-repression of P21 and Bax, and induction of cell cycle arrest/apoptosis, leading to cancer prevention. Other epigenetic mechanisms, including DNA methylation, histone methylation and non-coding RNA also appear to be impacted with SFN. This work suggests that phytochemical may have the ability to alter epigenetic events that lead to disease prevention. In human supplementation trials, we have directly compared the effects of the “whole food” (broccoli sprouts) to commercially available supplements. We have found a significant decrease in bioavailability and impact on HDACs with supplements compared to the whole food. Surprisingly, even when supplements are pre-treated with myrosinase, the release of sulforaphane from its glucosinolate precursors in the supplement is limited. These studies are significant because of the potential to qualify or change recommendations for high-risk prostate cancer patients and thereby increase their survival through simple dietary choices incorporating easily accessible foods into their diets. These mechanistic pre-clinical studies have provided a strong scientific foundation for on-going human clinical trials. | |