Molecular and Cellular Biology Program Oregon State University, Corvallis, OR, USA. Department of Nutrition and Exercise Sciences Oregon State University, Corvallis, OR, USA.
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables such as broccoli. The ability of SFN to inhibit histone deacetylase (HDAC) enzymes may be one mechanism by which it acts as a chemoprevention agent. The ability of a chemopreventive agent to specifically cause cytotoxicity in cancer and not normal cells is an important factor in determining its safety and clinical relevance.
We characterized the effects of SFN in normal (PrEC), benign hyperplasia (BPH1) and cancerous (LnCap and PC3) prostate epithelial cells. We observed that 15 μM SFN selectively induced cell cycle arrest and apoptosis in BPH1, LnCap and PC3 cells but not PrEC cells. SFN treatment also selectively decreased HDAC activity, and Class I and II HDAC proteins, increased acetylated histone H3 at the promoter for P21, induced p21 expression and increased tubulin acetylation in prostate cancer cells. HDAC6 over-expression was able to reverse SFN-induced cyotoxicity. In PrEC cells, SFN caused only a transient reduction in HDAC activity with no change in any other endpoints tested. The differences in sensitivity to SFN in PrEC and PC3 are likely not due to differences in SFN metabolism or differences in phase 2 enzyme induction.
SFN exerts differential effects on cell proliferation, HDAC activity and downstream targets in normal and cancer cells.
Written by:
Clarke JD, Hsu A, Yu Z, Dashwood RH, Ho E.
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Reference: Mol Nutr Food Res. 2011 Mar 4. Epub ahead of print.
doi: 10.1002/mnfr.201000547
PubMed Abstract
PMID: 21374800
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