Selenium is a Chemotherapeutic Agent for the Treatment of Prostate Cancer
Abstract
A large body of data suggests that selenium supplementation may be used as a chemopreventive strategy to reduce the risk of prostate cancer. In spite of this little is known regarding the use of selenium as a cancer therapy. High doses of selenite can deplete cells of the primary intracellular antioxidant glutathione and generate superoxide. The net effect of the metabolism of selenite is a profound alteration in the cellular redox status and generation of potentially lethal reactive oxygen species. We have characterized the tumor-selective killing properties of selenite in patient-matched pairs of normal and malignant prostate cells and demonstrated the ability of selenite to sensitize prostate cancer cells to ?-irradiation both in vitro and in vivo. Importantly we found that selenite does not sensitize intestinal and rectal mucosa to radiation in vivo using an intestional crypt stem cell survival assay. Recently we have also demonstrated that selenite inhibits androgen receptor expression and activity via a redox mechanism involving GSH superoxide and a redox sensitive transcription factor Sp1. The primary goal of this proposal was to generate pre-clinical data supporting the concept that selenite might be a novel chemotherapeutic agent for prostate cancer. Currently we are planning a phase I/II trial of selenite in patients with hormone refractory prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2007
- Accession Number
- ADA486154
Entities
People
- Susan J. Knox
Organizations
- Stanford University