CALPAIN INHIBITOR-INDUCED APOPTOSIS IN HUMAN PROSTATE ADENOCARCINOMA CELLS

Although it has been shown that calpains may play a positive role in c ausing apoptosis of T cells, we report here that, on the contrary, the inhibition of calpain-like activities can induce apoptosis in human p rostate cancer cells. Two calpain inhibitors were used to test growth response on prostate cancer cells and showed remarkable cytotoxicity. The cytotoxicity was due to apoptosis as judged by large genomic DNA f ragmentation, chromatin condensation and nuclear fragmentation. Furthe rmore, using gel band shift assays we have demonstrated that calpain i nhibitor 1 causes a prolonged elevation of AP-1 protein activity in hu man prostate cancer cells. The elevation of AP-1 activity appears to b e specific, because calpain inhibitor 1 only stimulates AP-1 but not A P-2 and SP-1 activities. We postulate that the sustained increase in A P-1 activity may be involved in apoptosis induced in prostate cells by calpain inhibitors. Our study thus suggests that calpain-like activit y may be a potentially therapeutic target for cancer. (C) 1995 Academi c Press, Inc.