Calpain inhibitor-induced apoptosis in human prostate adenocarcinoma cells.
Although it has been shown that calpains may play a positive role in causing apoptosis of T cells, we report here that, on the contrary, the inhibition of calpain-like activities can induce apoptosis in human prostate 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 fragmentation, chromatin condensation and nuclear fragmentation. Furthermore, using gel band shift assays we have demonstrated that calpain inhibitor 1 causes a prolonged elevation of AP-1 protein activity in human prostate cancer cells. The elevation of AP-1 activity appears to be specific, because calpain inhibitor 1 only stimulates AP-1 but not AP-2 and SP-1 activities. We postulate that the sustained increase in AP-1 activity may be involved in apoptosis induced in prostate cells by calpain inhibitors. Our study thus suggests that calpain-like activity may be a potentially therapeutic target for cancer.
Zhu
W
W
Department of Urology, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Murtha
P E
PE
Young
C Y
CY
D000230:Adenocarcinoma; D017209:Apoptosis / Q000187:drug effects*; D002154:Calpain / Q000037:antagonists & inhibitors*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003978:Diazomethane / Q000031:analogs & derivatives* / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011471:Prostatic Neoplasms; D016329:Sp1 Transcription Factor / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D009842:Oligopeptides; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C090218:benzyloxycarbonylleucyl-leucyl-tyrosine diazomethyl ketone; C039304:calpain inhibitors; D003978:Diazomethane; D002154:Calpain; D004121:Dimethyl Sulfoxide