| Cardiotoxin III induces apoptosis in K562 cells through a mitochondrial-mediated pathway. | |
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MedLine Citation:
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PMID: 16026508 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sheng-Huei Yang; Ching-Ming Chien; Mei-Chin Lu; Yu-Jhang Lu; Zchong-Zcho Wu; Shinne-Ren Lin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology Volume: 32 ISSN: 0305-1870 ISO Abbreviation: Clin. Exp. Pharmacol. Physiol. Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-07-19 Completed Date: 2006-06-09 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0425076 Medline TA: Clin Exp Pharmacol Physiol Country: Australia |
Other Details:
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Languages: eng Pagination: 515-20 Citation Subset: IM |
Affiliation:
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Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan ROC. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Caspase 3 Caspase 9 Caspases / metabolism Cell Survival / drug effects Cobra Cobra Cardiotoxin Proteins / chemistry, pharmacology* DNA Fragmentation / drug effects Dose-Response Relationship, Drug Flow Cytometry / methods Humans Hydrogen Peroxide / metabolism Intracellular Fluid / drug effects, metabolism K562 Cells Mitochondria / physiology* Signal Transduction / drug effects, physiology |
| Chemical | |
Reg. No./Substance:
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0/Cobra Cardiotoxin Proteins; 0/cardiotoxin III, Naja naja atra; 7722-84-1/Hydrogen Peroxide; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP9 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases |
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