Cardiotoxin III-induced apoptosis is mediated by Ca2+-dependent caspase-12 activation in K562 cells.
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 microM), a chelator of intracellular Ca2+. 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 micro-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 Ca2+ influx, then activated caspase-12 and JNK through micro-calpain-independent cascade, and consequently caused apoptosis.
Yang
Sheng-Huei
SH
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
Chien
Ching-Ming
CM
Chang
Long-Sen
LS
Lin
Shinne-Ren
SR
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D053454:Caspase 12 / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004179:Cobra Cardiotoxin Proteins / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells
D002614:Chelating Agents; D004179:Cobra Cardiotoxin Proteins; D004791:Enzyme Inhibitors; C082202:cardiotoxin III, Naja naja atra; C506444:CASP12 protein, human; D053454:Caspase 12; D053148:Caspase 3; D053453:Caspase 9; D002118:Calcium