Development of Novel Bifunctional Compounds that Induce Apoptosis in Prostate Cancer Cells
Abstract
We have designed and synthesized a novel compound (I ip) 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 lip is able to trigger apoptosis in target cells. One approach we are taking is to prepare structural analogs of lip that have increased or decreased abilities to cause apoptosis in LNCaP cells. Methods have been developed that will permit us to determine the fates of lIP-DNA adducts in treated cells as well as in target and nontarget tissues in xenograft mouse models of human prostate cancer. 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 lip may have clinical potential for the treatment of human tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2006
- Accession Number
- ADA454067
Entities
People
- John M. Essigmann
Organizations
- Massachusetts Institute of Technology