Title | 3,3'-Diindolylmethane, but not indole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Beaver LM, Yu T-W, Sokolowski EI, Williams DE, Dashwood RH, Ho E |
Journal | Toxicol Appl Pharmacol |
Volume | 263 |
Issue | 3 |
Pagination | 345-51 |
Date Published | 2012 Sep 15 |
ISSN | 1096-0333 |
Keywords | Androgens, Anticarcinogenic Agents, Cell Line, Tumor, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21, Gene Expression Regulation, Neoplastic, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Indoles, Male, Prostatic Neoplasms |
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. |
DOI | 10.1016/j.taap.2012.07.007 |
Alternate Journal | Toxicol. Appl. Pharmacol. |
PubMed ID | 22800507 |
PubMed Central ID | PMC3428467 |
Grant List | CA122959 / CA / NCI NIH HHS / United States P01 CA090890 / CA / NCI NIH HHS / United States P30 ES00210 / ES / NIEHS NIH HHS / United States R01 CA080176 / CA / NCI NIH HHS / United States CA90890 / CA / NCI NIH HHS / United States R01 CA122906 / CA / NCI NIH HHS / United States CA80176 / CA / NCI NIH HHS / United States R29 CA065525 / CA / NCI NIH HHS / United States R01 CA065525 / CA / NCI NIH HHS / United States CA122906 / CA / NCI NIH HHS / United States R01 CA122959 / CA / NCI NIH HHS / United States CA65525 / CA / NCI NIH HHS / United States P30 ES000210 / ES / NIEHS NIH HHS / United States |