CLP induces apoptosis in human leukemia K562 cells through Ca(2+) regulating extracellular-related protein kinase ERK activation.
The cyclic lipopeptide (CLP) has been known to inhibit proliferation and induce apoptosis in cancer cells. However, the molecular mechanisms involved in CLP-induced apoptosis are still uncharacterized in human leukemic K562 cells. The current study investigated the molecular mechanism of action of CLP, purified from Bacillus natto T-2. CLP-induced a sustained increase in concentration of intracellular Ca(2+). This increase in [Ca(2+)]i was associated with CLP-induced cell apoptosis and ERK phosphorylation. CLP-induced cell apoptosis was reversed by PD98059 (an inhibitor of ERK), but not by SB203580 (an inhibitor of p38) and SP200125 (an inhibitor of JNK), suggesting that the action of CLP on K562 cells was via ERK, but not via p38 and JNK. On the other hand, pretreatment with Bapta-AM, a well-known calcium chelator, partially blocked CLP-induced apoptosis, indicating that the elevation of [Ca(2+)]i may play an important role in the apoptosis. Collectively, in K562 cells, CLP-induced an increase in [Ca(2+)]i which evoked ERK phosphorylation. This ERK phosphorylation subsequently activated Bax, cytochrome c and caspase-3 leading to apoptosis.
Wang
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CL
Department of Microbiology, College of Life Science, Nankai University, Tianjin, China.
Ng
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TB
Cao
X H
XH
Jiang
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Liu
Z K
ZK
Wen
T Y
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Liu
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D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D020014:K562 Cells; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D055666:Lipopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis
D001426:Bacterial Proteins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D019253:Proto-Oncogene Proteins c-bcl-2; C524483:cyclic lipopeptide, Bacillus subtilis; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D002118:Calcium