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 PCa cells by methyl selenium (Se)/selenol We hypothesized that methyl inhibits PI3K-AKT survival pathway leading to the activation of caspase-dependent apoptosis execution in PCa cells We have in the reporting period refined a methylselenol generation system based on methioninase with selenomethionine as substrate (Wang et al, MoL Carcinogenesis, 2002) and studied the association of protein kinases and effects of PI3K inhibitors for apoptosis induction in DU145 cells by methyl Se and selenite (Jiang et al, Mol. Cancer Therapeutics, 2002). We compared the apoptosis responses of DU145 (androgen independent and mutant p53) and LnCaP (androgen dependent, wild type p53) PCa cell lines to methyl Se/selenol and to selenite. The LNCaP cells are PTEN mutant and possess high basal AKT activity and are more resistant to apoptosis induction by methyl Se, but was not cross resistant to cell death induction by selenite (AACR abstract, 2003). These studies lend additional credence to the role of PbK-AKT in apoptosis signaling induction by the methyl Se pool. Furthermore, we have discovered a caspase-dependent apoptosis response induced by selenite in LNCaP cells, which is distinct from the lack of caspase involvement in DU145 cells after selenite exposure. This led to a hypothesis that p53 phosphorylation may play a crucial role in mediating apoptosis induced by a genotoxic Se agent through caspase-mediated execution (AACR Abstract, 2003). We will investigate additional cell lines for correlation between P13K/AKT status and apoptosis sensitivity to methyl Se as well as p53 status and caspase-dependency for apoptosis induction by selenite in the next year.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2003
- Accession Number
- ADA414816
Entities
People
- Junxuan Lu