Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity
Abstract
We hypothesized that dehydroepiandrosterone metabolites or their synthetic derivatives are able to bind to the androgen receptor with low, if any, agonist activity and thus function as better antiandrogens than currently available ones. We previously identified three potential compounds with marginal androgenic activity. Using different prostate cancer cell lines, we showed that these compounds could inhibit androgen-induced growth of androgen receptor-positive tumors in vitro. In tolerance tests, the mice appeared to suffer from no adverse effects from injections of the steroids. We then assessed the anti-tumor activities of these compounds in mouse xenograft models for prostate cancer. Inconsistent with our in vitro data, the dehydroepiandrosterone metabolites only slightly reduced the growth of inoculated tumors as well as the expression of angiogenesis- and metastasis-related genes in the tumors. Thus, we plan to perform further in vivo experiments (e.g. higher doses of the compounds, different cell lines).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA613857
Entities
People
- Hiroshi Miyamoto
Organizations
- University of Rochester