Up-regulation of Bax and endonuclease G, and down-modulation of Bcl-X(L) involved in cardiotoxin III-induced apoptosis in K562 cells.
- Author:
Sheng Huei YANG
1
;
Ching Ming CHIEN
;
Mei Chin LU
;
Yi Hsiung LIN
;
Xiu Wei HU
;
Shinne Ren LIN
Author Information
1. Faculty of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. shreli@cc.kmu.edu.tw
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
bcl-2-associated X protein;
cardiotoxin III, Naja naja atra;
caspase;
endonuclease G;
K562 cells
- MeSH:
bcl-X Protein/*metabolism;
bcl-2-Associated X Protein/*metabolism;
Up-Regulation/drug effects;
Reactive Oxygen Species/metabolism;
Mitochondrial Proteins/metabolism;
Mitochondrial Membranes/drug effects;
Membrane Potentials/drug effects;
K562 Cells;
Inhibitor of Apoptosis Proteins/metabolism;
Humans;
Endodeoxyribonucleases/*metabolism;
Down-Regulation/drug effects;
Direct Lytic Factors/*pharmacology;
Cytochromes c/metabolism;
Cell Proliferation/drug effects;
Caspases/metabolism;
Apoptosis/*drug effects
- From:Experimental & Molecular Medicine
2006;38(4):435-444
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-induced K562 cell apoptosis was confirmed by DNA fragmentation (DNA ladder, sub-G1 formation) and phosphatidylserine (PS) externalization with an IC50 value of 1.7 mug/ml at 48 h. A mechanistic analysis demonstrated that CTX III-induced apoptotic cell death was accompanied by up-regulation of both Bax and endonuclease G (Endo G), and downregulation of Bcl-X(L). CTX III had no effect on the levels of Bcl-2, Bid, XIAP survivin, and AIF proteins. CTX III treatment caused loss of the mitochondrial membrane potential (delta psi m), release of mitochondrial cytochrome c to the cytosol, and activation of both caspase-9 and -3. CTX III-induced apoptosis was significantly blocked by the broad-spectrum caspase inhibitor Z-VAD-FMK. However, CTX III did not generate reactive oxygen species (ROS) and antioxidants, including N-acetylcysteine and catalase, did not block CTX III-induced apoptosis in K562 cells. Modulation of Bax, Bcl-X(L), and the Endo G proteins, release of mitochondrial cytochome c, and activation of caspase-3 and -9 all are involved in the CTX III-triggered apoptotic process in human leukemia K562 cells.
