Sulforaphane inhibits HDAC activity in prostate cancer cells, retards growth of PC3 xenografts, and inhibits HDAC activity in vivo

Abstract

Drugs classified as histone deacetylase (HDAC) inhibitors have shown promise as cancer chemopreventive and therapeutic agents. Recently, we reported that HDAC inhibition might be a novel mechanism of chemoprotection by sulforaphane (SFN), a compound found in cruciferous vegetables. In the present study, we sought to identify the effects of SFN in normal prostate epithelial cells (PrEC) and androgen-independent prostate cancer cells (PC3). Addition of 15 μM SFN inhibited HDAC activity and induced accumulation of acetylated histones in both normal and prostate cancer cells. However, SFN induced expression of p21 and a G2/M arrest only in PC3 cells, with no effect in PrEC. Thus, similar to other HDAC inhibitors, SFN exhibited selective anti-proliferative effects to cancer cells. Secondly, we examined the effects of SFN on HDAC inhibition and prostate chemoprevention in vivo using a xenograft model. Dietary SFN (~7.5 μmol per day) caused a significant decrease in HDAC activity and increase in histone acetylation in the xenografts, prostates and peripheral blood mononuclear cells (PBMC) and suppressed the growth of PC3 xenografts. Thus, consumption of SFN in the diet was able to inhibit HDAC activity in circulating blood cells and prostate, and retard prostate tumor growth in vivo. These findings provide evidence that one potential mechanism by which SFN acts as a cancer chemopreventive agent is by the inhibition of HDAC activity. This work was supported by: CA66525 (RHD), CA80176 (RHD), CA90890 (RHD) and CA107693 (EH).