#C171 Anti-Prostate Cancer Activity of Diindolylmethane (DIM): A Second Generation Chemopreventive Agent. Ashok T. Badithe, Venkata Garikapaty, Yuangen Chen, Abraham Mittelman, Raj K. Tiwari, New York Medical College, Valhalla, NY. Diindolylmethane (DIM) is an acid-catalyzed dimer of indole-3-carbinol (I3C). These compounds are derived from the parent compound glucobrassicin found in cruciferous vegetables such as cabbage, broccoli and brussels sprouts. While the chemopreventive and anti-carcinogen efficacy of I3C were clearly shown in several animal models, in some carcinogen-induced models I3C shows a promotional activity in tissues such as liver, thyroid and colon. DIM is a second-generation chemoprevention agent that is 3-5 fold more efficacious than I3C and does not have any adverse cancer promotional effects. Both I3C and DIM have not been comprehensively evaluated as chemopreventive/anticancer agents in prostate cancer. We examined the anticancer effect of I3C on the transplantable androgen non-responsive metastatic rat prostate cancer cell line, MAT-LyLu (MLL), in Copenhagen rats. I3C injected i.v. (0.1 mg /Kg body weight) and i.p. (0.4 mg/Kg) 2X weekly showed significant tumor reduction both in terms of tumor incidence and rate of tumor growth. The latency of tumor induction was increased by more than seventy five percent. Fifty percent of the animals treated with I3C were tumor free and more importantly, showed significant reduction in number of lung metastases. Downregulation of cyclin D1 and cyclin dependent kinase cdk4 were observed in MAT-LyLu cells treated with I3C or DIM. The levels of PI3 Kinase, Bcl2, Bax and phosphorylated Akt did not change in response to I3C. However, the levels of total Akt and p38 showed a significant downregulation with a complete obliteration of Akt levels and a greater than 50% inhibition in p38 levels. Downregulation of Akt was also observed when MLL cells were exposed to DIM. The anti-cancer effect of DIM/I3C is mediated through inhibition of signal transduction pathways, particularly the Akt pathway leading to cell cycle inhibition and/or induction of apoptosis. These studies clearly demonstrate an anticancer effect for I3C and DIM in the prevention and treatment of prostate cancer, specifically for metastatic disease and that DIM as a compound that does not cause any adverse effect may be the chemopreventive agent to be developed clinically. Frontiers in Cancer Prevention Research, 2003 AACR Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.