Cardiotoxin III-induced apoptosis is mediated by Ca2+-dependent caspase-12 activation in K562 cells

✍ Scribed by Sheng-Huei Yang; Ching-Ming Chien; Long-Sen Chang; Shinne-Ren Lin

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 289 KB
• Volume: 22
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/jbt.20231

✦ Synopsis

Abstract

Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. When K562 cells were treated with CTX III, cytosolic calcium concentration was rapidly and persistently increased. This CTX III‐induced cell death was partially reversed by pretreatment with BAPTA/AM (20 µM), a chelator of intracellular Ca^2+^. Moreover, CTX III‐induced apoptotic signals, such as caspase‐12 and c‐Jun N‐terminal kinase (JNK) activation, were induced in a time‐dependent manner and inhibited by BAPTA/AM. In contrast, the neutral protease µ‐calpain, a key enzyme in endoplasmic reticulum (ER) stress‐related apoptosis via caspase‐12 activation, was unchanged during apoptosis. Taken together, our findings suggest CTX III‐induced apoptosis is triggered by Ca^2+^ influx, then activated caspase‐12 and JNK through µ‐calpain‐independent cascade, and consequently caused apoptosis. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:209–218, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20231