Dehydroepiandrosterone Derivatives as Potent Antiandrogens with Marginal Agonist Activity
Abstract
We hypothesized that dehydroepiandrosterone (DHEA) 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. Nonetheless, we were aware that these compounds also possessed estrogenic activity that may cause severe side effects if used in vivo. Using different prostate cancer cell lines, we evaluated androgenic/antiandrogenic effects of the three steroids on cell proliferation/survival/apoptosis and expression of several molecules related to cell growth/angiogenesis/metastasis. We found that these compounds indeed exhibited antiandrogenic activities, although they were not always significant. Our results suggest that these compounds are superior to current antiandrogens, in terms of androgenic and antiandrogenic properties in prostate cancer cells in vitro. We also established LNCaP sublines after long-term treatment with each compound. Additionally, screening of DHEA derivatives resulted in identification of a new compound that shows marginal androgenic/strong antiandrogenic activity as well as marginal estrogenic activity. We continue to assess the effects of these four potential compounds in prostate cancer in vitro and in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2010
- Accession Number
- ADA542465
Entities
People
- Hiroshi Miyamoto
Organizations
- University of Rochester