Development of Novel Bifunctional Compounds that Induce Apoptosis in Prostate Cancer Cells; Annual rept. 1 Mar 2007-28 Feb 2008

摘要

We have designed and synthesized a novel compound (11 beta) that efficiently triggers apoptosis in prostate cancer cells such as LNCaP. This bifunctional compound was designed to form DNA adducts that are camouflaged by the androgen receptor making them less readily repaired in AR+ prostate cancer cells. The aims of our studies are to investigate the mechanisms by which 11 beta is able to trigger apoptosis in target cells. Methods have been developed that permit us to determine the fates of 11 beta-DNA adducts in treated cells in culture as well as in tumors growing in animal models. Another objective is to identify the signaling events that lead from DNA adducts to activation of the apoptotic program. Finally we have obtained encouraging results from animal experiments that indicate that molecules such as 11 beta may have clinical potential for the treatment of human tumors.