Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal and prostate cancer cells

Abstract

Epidemiological data indicate that a diet high in cruciferous vegetables may lower the overall risk of prostate cancer. The ability of sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, to inhibit histone deacetylases (HDAC) may be one mechanism by which it acts as a chemoprevention agent. Interestingly, the antiproliferative effects of pharmacological HDAC inhibitors are specific to cancer cells. The objective of this study was to compare the effects of SFN on HDAC inhibition and downstream molecular targets in both normal (PrEC) and cancerous (PC3) prostate epithelial cells. We hypothesize that SFN will act similar to pharmacological HDAC inhibitors and selectively target cancer cells. In PC3, SFN decreased HDAC activity, decreased HDACs 3, 6, and 8, increased acetylated histone H3 at the promoter for p21, induced p21 expression and increased tubulin acetylation. These data suggest that SFN targets both Class I and II HDACs in prostate cancer cells. In PrEC, SFN caused only a transient reduction in HDAC activity with no change in any other endpoints tested. SFN also induced selective cell cycle arrest and apoptosis in PC3 but not PrEC. We conclude that SFN exerts differential effects on HDAC activity and downstream targets in normal and cancer cells. Together, these data highlight the potential of SFN, a dietary HDAC inhibitor as an effective chemoprevention agent. Funded by NIHCA122906.Grant Funding Source: NIHCA122906