Contributions of autophagic and apoptotic mechanisms to CrTX-induced death of K562 cells.
Previous studies reported that the neurotoxin, Crotoxin, isolated from the venom of South American rattlesnake had potent anti-tumor activity. Here, we investigated the involvement of autophagy and apoptosis in the Crotoxin-induced death of chronic myeloid leukemia cell line K562 cells. The neurotoxin dose dependently inhibited the viability of K562 cells. Crotoxin stimulated the autophagic activity as evidenced by the appearance of punctuate monodansylcadaverine (MDC) fluorescence staining in the cytoplasm and increased the formation of autophagosomes. Crotoxin caused the collapse of the mitochondrial membrane potential, release of cytochrome c and activation of caspase-3. Caspase inhibitors attenuated Crotoxin-induced K562 cell death, while blockage of autophagy maturation with 3-methyladenine (3-MA) and NH4Cl potentiated the neurotoxin's cytotoxicity. These results suggest that an apoptotic mechanism contributes to the Crotoxin-induced death of K562 cells, while the activation of autophagy delays neurotoxin-induced apoptosis.
Department of Pharmacology, Soochow University School of Medicine, Suzhou Institute of Chinese Materia Medica, 708 Ren Min Road, Suzhou 215007, People's Republic of China.
Ci-Hui
CH
Yan
Zhong-Qin
ZQ
Liang
Zhen-Lun
ZL
Gu
Ya-Ping
YP
Yang
Paul
P
Reid
Zheng-Hong
ZH
Qin
D000225:Adenine / Q000031:analogs & derivatives; D000590:Amino Acid Chloromethyl Ketones; D000643:Ammonium Chloride; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D003439:Crotoxin / Q000494:pharmacology*; D045304:Cytochromes c / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D020014:K562 Cells; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009842:Oligopeptides; D014617:Vacuoles / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000643:Ammonium Chloride; C025946:3-methyladenine; D003439:Crotoxin; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000225:Adenine