Mitochondrial involvement in Casodex-induced cell death in prostate cancer

Anti-androgens such as Casodex are designed to treat advance stage prostate cancer by interfering with androgen receptor-mediated cell survival and initiating cell death. We have treated hormone-dependent, nonmetastatic LNCaP human prostate cells with 0-100muM Casodex. These treatments induce cell death in 20-60% of the cells by 48h. This is accompanied by mitochondrial membrane permeabilization but sustained mitochondrial dehydrogenase activity. Over-expression of Bcl-2 in LNCaP cells attenuates the induction of cell death by TNF-alpha but not Casodex, suggesting that nutochondria depolarization is not required for the induction of cell death by Casodex. Taken together, these data support the hypothesis that Casodex induces cell death in an indirect and incomplete fashion that results in an extended lag phase of cell survival after treatment.