Involvement of p38 and c-Jun N-terminal protein kinase in cardiotoxin III-induced apoptosis of K562 cells.

Cardiotoxin III (CTX III), a 60-amino acid basic polypeptide isolated from Naja venom, showed potential therapeutic activity toward cancer cells. Here we report that CTX III inhibited proliferation of human leukemia K562 cells by G2/M phase arresting and apoptosis which was associated with the activation of caspase-8 and cytochrome c release as well as the p38 and c-Jun N-terminal protein kinase (JNK) phosphorylation signaling pathway. We further demonstrated that daily administration of CTX III for 2 d to chicken chorioallantoic membrane (CAM) bearing tumours derived from the CAM at E10 administration of K562 cells resulted in inhibition of the tumours in vivo. Importantly, this in vivo inhibition was also associated with caspase-8 activation and cytochrome c release. Our results suggest that CTX III-induced apoptosis is mediated via the p38 and JNK pathway as well as the caspase-8-dependent Bid-Bax pathway in human K562 cells.