Cardiotoxin III induces apoptosis in K562 cells through a mitochondrial-mediated pathway.
1. Cardiotoxin (CTX) III is a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom. This is the first report on the mechanism of the anticancer effect of CTX III on human leukaemia K562 cells. 2. Cardiotoxin III was found to inhibit the growth of K562 cells in a time- and dose-dependent manner, with an IC(50) value of 1.7 mug/mL, and displayed several features of apoptosis, including apoptotic body formation, an increase in the sub-G(1) population, DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage. 3. Investigation of the mechanism of CTX III-induced apoptosis revealed that treatment of K562 cells with CTX III resulted in the loss of mitochondrial membrane potential, cytochrome c release from mitochondria into the cytosol and activation of caspase-9 and caspase-3 and the subsequent cleavage of the caspase-3 substrate PARP; however, CTX III did not generate reactive oxygen species (ROS). 4. Taken together, the results indicate that CTX III induces apoptosis in K562 cells through an ROS-independent mitochondrial dysfunction pathway.
Yang
Sheng-Huei
SH
Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan ROC.
Chien
Ching-Ming
CM
Lu
Mei-Chin
MC
Lu
Yu-Jhang
YJ
Wu
Zchong-Zcho
ZZ
Lin
Shinne-Ren
SR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004179:Cobra Cardiotoxin Proteins / Q000737:chemistry / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017815:Elapidae; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D020014:K562 Cells; D008928:Mitochondria / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004179:Cobra Cardiotoxin Proteins; C082202:cardiotoxin III, Naja naja atra; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases