Purification And Antitumor Mechanism Of CTX-b From Naja Naja Atra Venom

Backgroud and purposesCytotoxins (CTXs), a group of highly basic polypeptides present abundantly in cobra venom (Naja naja atra), showed preferential cytotoxicity towards cancer cells. Until now, the molecular mechanism by which CTXs exert their cytotoxicity has remained unclear. It is widely accepted that the plasma membrane is a target of cytotoxins. Depending on its characteristic three-finger loop structure, CTXs penetrated into membranes to form pores, and thus induced its cytolytic effect. Recent results showed that CTXs were internalized to mitochondria within minutes and the toxin was capable of disrupting the mitochondria network (Wang, C. H. et al); Arseniev AS et al recently reported that cytotoxins from cobra venom penetrated readily into living cancer cells and accumulated markedly in lysosomes. The concentration-dependence of cytotoxin accumulation in lysosomes correlated well with their cytotoxic effects. These works indicated that mitochondria and lysosomes may be the primary targets of the lytic action of cytotoxins, direct damage to the plasma membrane may be a complementary mechanism.Recent studies showed that mitochondria played an essential role in the regulation of apoptosis. Damages to mitochondria results in mitochondrial permeability transition, and then induce the release of cytochrome c, which together with Apaf-1 (apoptotic protease activating factor-1) and dATP lead to the recruitment and activation of procaspase-9 which, in turn, activates downstream caspases, caspase -3, leading to apoptosis.Since CTXs could internalized to mitochondria within minutes, our interest...