Chemopreventative Phytochemical 3,3 '-Diindolylmethane Inhibits Histone Deacetylases In Prostate Cancer Cells

Increased consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. Indole‐3‐carbinol (I3C) and 3, 3′‐diindolylmethane (DIM), phytochemicals derived from cruciferous vegetables, have shown promise in inhibiting prostate cancer in experimental models. Histone deacetylase (HDAC) inhibition is an emerging target for cancer prevention and therapy. We sought to examine the effects of I3C and DIM on HDACs in prostate cancer cells. I3C had a minimal effect on cell proliferation and had no effect on HDAC activity or expression in androgen insensitive (PC‐3) prostate cancer cells. In contrast, DIM significantly decreased cell proliferation, HDAC activity, as well as HDAC2 and HDAC8 expression in PC‐3 cells. A trend of decreasing expression was observed for HDAC4 and HDAC6. Surprisingly, DIM treatment caused a significant reduction in acetylated histone H4 but an increase in acetylation of the HDAC6 target gene, tubulin. DIM also significantly inhibited HDAC activity in androgen sensitive LnCap cells. These results show that DIM inhibits HDAC activity and may contribute to the anti‐proliferative effects of DIM in the prostate. The ability of DIM to target aberrant epigenetic patterns, in addition to its effects on detoxification, may make it an effective chemopreventive agent by targeting multiple stages of prostate carcinogenesis.Grant Funding Source : P01CA090890