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 chemopreventative strategy to reduce the risk of prostate cancer. In spite of this, little is known about the use of selenium as a cancer therapy. The inorganic form of selenium, selenite, undergoes thiol-dependent reduction to selenide, which supplies selenium for the synthesis of selenoproteins. At lower concentrations, the major effects of selenite are related to its role as a micronutrient. However, at higher concentrations, selenite may become toxic. Excessive selenite metabolism depletes cells of the primary intracellular antioxidant, glutathione, and generates 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. The authors characterized the response of androgen-dependent LAPC-4 prostate cancer cells, as well as patient-matched pairs of normal and malignant prostate cells to selenite. Selenite-induced growth inhibition and apoptosis were correlated with changes in Bcl-2 family member expression, altered intracellular GSH status, and MnSOD expression. They also examined the ability of selenite to sensitize prostate cancer cells to gamma irradiation. The primary goal of this proposal was to generate preclinical data supporting the concept that selenite might be useful as a novel chemotherapeutic agent alone or in combination with radiation therapy to treat prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA433911
Entities
People
- Susan J. Knox
Organizations
- Stanford University