Dietary Methionine Restriction: Novel Treatment for Hormone Independent Prostate Cancer
Abstract
Many studies have shown that methionine restriction inhibits growth of a variety of human tumor xenografts, including prostate cancers. In contrast, methionine restriction is relatively well tolerated by normal host tissues. The overall goal of the current project is to clarify the molecular mechanisms by which methionine restriction inhibits tumor growth. During the first year of support, we focused on Specific Aim 1, which is to determine whether methionine restriction increases oxidative stress in human prostate cancer cells. We used an established biochemical assay to measure intracellular glutathione levels and glutathione export. The assay enabled us to distinguish reduced glutathione (GSH) from glutathione disulfide (GSSG), an oxidized form. We found that methionine restriction had no appreciable affect on total intracellular glutathione content in PC-3 prostate cancer cells, or on the ratio of GSH/GSSG or glutathione export from those cells. We plan to confirm these results with additional control experiments with known inhibitors of glutathione synthesis and normal rat hepatocytes. If confirmed, these results indicate that methionine auxotrophy of tumors is probably not related to the role of methionine in glutathione synthesis and homeostasis, but rather to its role as a methyl donor, as proposed for Specific Aim 3.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA406966
Entities
People
- Daniel E. Epner
Organizations
- Baylor College of Medicine