Sulforaphane (SFN) is an
isothiocyanate found in cruciferous vegetables, such as broccoli and broccoli sprouts. This anticarcinogen was first identified as a potent inducer of Phase 2 detoxification
enzymes, but evidence is mounting that SFN also acts through epigenetic mechanisms. SFN has been shown to inhibit
histone deacetylase (HDAC) activity in human colon and
prostate cancer lines, with an increase in global and local
histone acetylation status, such as on the promoter regions of P21 and bax genes. SFN also inhibited the growth of
prostate cancer xenografts and spontaneous
intestinal polyps in mouse models, with evidence for altered
histone acetylation and HDAC activities in vivo. In human subjects, a single ingestion of 68 g broccoli sprouts inhibited HDAC activity in circulating peripheral blood mononuclear cells 3-6 h after consumption, with concomitant induction of
histone H3 and H4 acetylation. These findings provide evidence that one mechanism of
cancer chemoprevention by SFN is via epigenetic changes associated with inhibition of HDAC activity. Other dietary agents such as
butyrate,
biotin,
lipoic acid, garlic organosulfur compounds, and metabolites of
vitamin E have structural features compatible with HDAC inhibition. The ability of dietary compounds to de-repress epigenetically silenced genes in
cancer cells, and to activate these genes in normal cells, has important implications for
cancer prevention and
therapy. In a broader context, there is growing interest in dietary
HDAC inhibitors and their impact on epigenetic mechanisms affecting other
chronic conditions, such as
cardiovascular disease, neurodegeneration and aging.