Induction of apoptosis in human leukemia K562 cells by cardiotoxin III.
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. CTX III was found to inhibit the growth of K562 cells in a time-and dose-dependent manner with IC50 value of 1.7 microg/ml, and it displayed several features of apoptosis including apoptotic body formation, increase of sub G1 population, DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage. Investigation of the mechanism of CTXIII--induced apoptosis revealed that the treatment of K562 cells with CTX III resulted in the activation of caspase-9, caspase-3 and subsequent cleavage of its substrate PARP and that CTXIII was also associated with an early release of cytochrome c from the mitochondria. These results suggest that CTX III may induce apoptosis through a mitochondria- and caspase-dependent mechanism.
Yang
Sheng-Huei
SH
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan 807, ROC.
Lu
Mei-Chin
MC
Chien
Ching-Ming
CM
Tsai
Chia-Houg
CH
Lu
Yu-Jhang
YJ
Hour
Tzyh-Chyuan
TC
Lin
Shinne-Ren
SR
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004179:Cobra Cardiotoxin Proteins / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D008928:Mitochondria / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors
D004179:Cobra Cardiotoxin Proteins; C082202:cardiotoxin III, Naja naja atra; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases