Methylselenium and Prostate Cancer Apoptosis
Abstract
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 (Se)/selenol. We hypothesized that methyl selenium inhibits survival pathway leading to the activation of caspase-dependent apoptosis execution in PCa cells. The specific aims are to delineate the caspase-mediated execution pathways of apoptosis (Objective 1) and to critically test the role of PI(SUB 3)K-AKT survival pathway in apoptosis signaling (Objective 2) induced by methyl Se/selenol. We have performed experiments pertinent to these two objectives. Specifically, we established an inverse correlation between AKT activity and the sensitivity to MSeA in 3 PCa cell lines; characterized the effects of PI(SUB 3)K and AKT inhibitors as well as MEK-ERK inhibitor on MSeA -induced apoptosis; established the caspase-dependence for apoptosis execution in LNCaP cells induced by MSeA when combined with inhibitors; and showed greater impact on mitochondria cytochrome c release by PI(SUB 3)K-AKT pathway than ERK; established stable activated AKT transfectant DU145 clones and showed a AKT-dose-dependent increase in resistance to MSeA. Finally we also established the specificity of PI(sub 3)K-AKT and ERK regulation of MSeA induced death was not observed in selenite-induced death in LNCaP cells. These results have been published in Carcinogenesis, 2005 (reprint).
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA443005
Entities
People
- Junxuan Lu
Organizations
- University of Minnesota