Methylselenium and Prostate Cancer Apoptosis; Final addendum rept. 4 Jan 2002-3 Jan 2008

摘要

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. The specific aim for the no-cost extension period is to define early signaling mechanisms induced by methylselenium for apoptosis and how and through what targets AKT regulates death signaling. We have identified BCl-xL, FLIP and survivin as early targets affected by MSeA. This was designed to follow up on a novel lead for using selenium as a chemosensitizer for cancer therapeutic drug-induced apoptosis in androgen independent PCa cells. Work accomplished: We have tested the functional significance of MSeA-induced down regulation of Bcl-xL and survivin through the ectopic expression of these two genes in DU145 cells and tested their impact on apoptosis induced by taxol. The results have been accepted for publication in Clinical Cancer Res. Re-print is appended for this addendum report.