Methylselenium and Prostate Cancer Apoptosis
Final rept. 4 Jan 2002-3 Jan 2007
MINNESOTA UNIV MINNEAPOLIS
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The purpose of this research is to gain a better understanding of the biochemical pathways and molecular targets for the selective induction of apoptosis signaling and execution of prostate cancer PCa cells by methyl selenium. We hypothesized that methyl selenium inhibits PI3K-AKT survival pathway leading to the activation of caspase-dependent apoptosis execution in PCa cells. Data generated support PI3K-AKT pathway activity as a determinant of the apoptosis sensitivity of PCa cells to a prototype methyl Se MSeA which can be further modulated by ERK12. AKT and ERK12 differentially modulated cytochrome c involvement in MSeA-induced extrinsic major and intrinsic caspase cascades. We have pursued a novel lead for using selenium as a chemosensitizer for cancer therapeutic drug-induced apoptosis in androgen independent PCa cells. We have also discovered a synergistic enhancement of apoptosis effect of TRAIL an anti-cancer biological by the genotoxic selenite through p53-mediated actions. The chemosensitizer activity of selenium is expected to improve quality of life of prostate cancer patients because of increased efficacy and reduced dosage needed. Seven publications are credited to the support by this grant award. Validation of these findings in animal models is currently in progress.
- Anatomy and Physiology
- Medicine and Medical Research