Development of Novel Bifunctional Compounds that Induce Apoptosis in Prostate Cancer Cells
Abstract
The objective of our research is to develop more effective therapeutics for the treatment of prostate cancers. One novel bifunctional compound (11beta) that we have prepared rapidly induces apoptosis in several prostate cancer cell lines in vitro. The 11beta compound contains a chemically reactive nitrogen mustard linked to a steroid moiety that binds with high affinity to the androgen and progesterone receptor proteins. This compound was designed to create DNA adducts that form tight complexes with these steroid receptors that make the adducts difficult to repair in prostate cancer cells. Preliminary studies of 11beta in cell culture indicated that its effects on prostate cancer cells were different from those of other alkylating agents used in chemotherapy. The apoptotic responses of prostate cancer cells suggested that the 11beta compound might be a useful agent for chemotherapy. The Specific Aims of our research are to understand the fate of 11beta-DNA adducts in treated cells and investigate the mechanisms that lead to apoptosis. We also proposed experiments to assess the antitumor potential of 11beta in animal models of human prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA437129
Entities
People
- John M. Essigmann
Organizations
- Massachusetts Institute of Technology