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 Pl3K-AKT 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 Pl3K-AKT survival pathway in apoptosis signaling (Objective 2) induced by methyl Se/selenol. We have continued experiments pertinent to these two objectives and have pursued a novel lead for methyl Se as a chemosensitizer for cancer therapeutic drugs in androgen independent PCa cells, which are very resistant to conventional chemotherapy. Specifically, we established the MSeA, but not selenite, enhanced apoptosis induced by 3 clinically relevant drugs, taxol, etoposide and CPT-11. We established that the enhancement was mediated by increased activation of caspases. We established a crucial role of the JNK pathway in mediating death signals from all three drugs. Key results were published in Clinical Cancer Res 2005. In the next year, we plan to investigate the role and interplay with Pl3K/AKT and ERK regulation of the chemosensitization by MSeA. These mechanistic investigations will lay ground work for future validation studies in vivo and translation from the bench to the bedside.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2006
- Accession Number
- ADA448522
Entities
People
- Junxuan Lu
Organizations
- University of Minnesota