CARDIOTOXIN III INDUCES APOPTOSIS IN K562 CELLS THROUGH A MITOCHONDRIAL-MEDIATED PATHWAY
Article first published online: 13 JUL 2005
Clinical and Experimental Pharmacology and Physiology
Volume 32, Issue 7, pages 515–520, July 2005
How to Cite
Yang, S.-H., Chien, C.-M., Lu, M.-C., Lu, Y.-J., Wu, Z.-Z. and Lin, S.-R. (2005), CARDIOTOXIN III INDUCES APOPTOSIS IN K562 CELLS THROUGH A MITOCHONDRIAL-MEDIATED PATHWAY. Clinical and Experimental Pharmacology and Physiology, 32: 515–520. doi: 10.1111/j.1440-1681.2005.04223.x
- Issue published online: 13 JUL 2005
- Article first published online: 13 JUL 2005
- Received 5 October 2004; revision 13 December 2004; accepted 24 January 2005.
- cardiotoxin III;
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 IC50 value of 1.7 μg/mL, and displayed several features of apoptosis, including apoptotic body formation, an increase in the sub-G1 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.