3,3'-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells.

Abstract

Increased consumption of cruciferous vegetables is associated with a reduced risk of developing prostate cancer. Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are phytochemicals derived from cruciferous vegetables that 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 human prostate cancer cell lines: androgen insensitive PC-3 cells and androgen sensitive LNCaP cells. I3C modestly inhibited HDAC activity in LNCaP cells by 25% but no inhibition of HDAC activity was detected in PC-3 cells. In contrast, DIM significantly inhibited HDAC activity in both cell lines by as much as 66%. Decreases in HDAC activity correlated with increased expression of p21, a known target of HDAC inhibitors. DIM treatment caused a significant decrease in the expression of HDAC2 protein in both cancer cell lines but no significant change in the protein levels of HDAC1, HDAC3, HDAC4, HDAC6 or HDAC8 was detected. Taken together, these results show that inhibition of HDAC activity by DIM may contribute to the phytochemicals' anti-proliferative effects in the prostate. The ability of DIM to target aberrant epigenetic patterns, in addition to its effects on detoxification of carcinogens, may make it an effective chemopreventive agent by targeting multiple stages of prostate carcinogenesis.

• Authors: Laura M Beaver, Tian-Wei Yu, Elizabeth I Sokolowski, David E Williams, Roderick H Dashwood, Emily Ho
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 263 Issue 3 Pg. 345-51 (Sep 15 2012) ISSN: 1096-0333 [Electronic] United States
• PMID: 22800507 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Androgens
• Anticarcinogenic Agents
• Cyclin-Dependent Kinase Inhibitor p21
• Histone Deacetylase Inhibitors
• Indoles
• indole-3-carbinol
• HDAC2 protein, human
• Histone Deacetylase 2
• Histone Deacetylases
• 3,3'-diindolylmethane

Topics

• Androgens (metabolism)
• Anticarcinogenic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• Histone Deacetylase 2 (genetics)
• Histone Deacetylase Inhibitors (pharmacology)
• Histone Deacetylases (drug effects, metabolism)
• Humans
• Indoles (pharmacology)
• Male
• Prostatic Neoplasms (drug therapy, pathology)