Up-regulation of Bax and endonuclease G, and down-modulation of Bcl-X(L) involved in cardiotoxin III-induced apoptosis in K562 cells
Experimental & Molecular Medicine
; : 435-444, 2006.
Article
在 En
| WPRIM
| ID: wpr-200505
Responsible library:
WPRO
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.
Key words
全文:
1
索引:
WPRIM
主要主题:
Down-Regulation
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Up-Regulation
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Reactive Oxygen Species
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Apoptosis
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K562 Cells
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Caspases
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Mitochondrial Proteins
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Cytochromes c
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Cell Proliferation
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Cobra Cardiotoxin Proteins
限制:
Humans
语言:
En
期刊:
Experimental & Molecular Medicine
年:
2006
类型:
Article