| Upregulation and activation of caspase-3 or caspase-8 and elevation of intracellular free calcium mediated apoptosis of indomethacin-induced K562 cells. | |
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MedLine Citation:
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PMID: 15265368 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: A nonsteroidal anti-inflammatory drug, indomethacin, has been shown to have anti-leukemic activity and induce leukemic cell apoptosis. This study was to elucidate the mechanism of indomethacin-induced K562 cell apoptosis. METHODS: K562 cells were grown in RPMI 1640 medium and treated with different doses of indomethacin (0 micromol/L, 100 micromol/L, 200 micromol/L, 400 micromol/L, 800 micromol/L) for 72 hours. The cells were harvested, and cell viability or apoptosis was analyzed using MTT assay and AO/EB stain, combining laser scanning confocal microscopy (LSCM) technique separately. For the localization and distribution of intracellular caspase-3 or caspase-8 protein, immunofluorescence assay was carried out. To reveal the activation of caspase-3 or caspase-8 in indomethacin-treated cells, Western blot detection was used. The change in intracellular free calcium was determined by Fluo-3/Am probe labeling combined with LSCM. RESULTS: Indomethacin could lead to K562 cell apoptosis and inhibit cell viability in a concentration-dependent manner. An increased expression of intracellular caspase-3 or caspase-8 was observed at higher doses of indomethacin (400 - 800 micromol/L). Western blot results showed upregulation and activation in both caspase-3 and caspase-8 protein. Under indomethacin intervention, the levels of intracellular free calcium showed a significant increase. Blocking the activity of cyclooxygenase did not abolish the effects of indomethacin on K562 cell apoptosis. CONCLUSIONS: Activation and upregulation of caspase-3 or caspase-8 protein were responsible for Indomethacin-induced K562 cell apoptosis. Variation of intracellular free calcium might switch on the apoptotic pathway and the proapoptotic effect of indomethacin might be cyclooxygenase-independent. |
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Authors:
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Guang-sen Zhang; Guang-biao Zhou; Chong-wen Dai |
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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: Chinese medical journal Volume: 117 ISSN: 0366-6999 ISO Abbreviation: Chin. Med. J. Publication Date: 2004 Jul |
Date Detail:
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Created Date: 2004-07-21 Completed Date: 2004-10-28 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7513795 Medline TA: Chin Med J (Engl) Country: China |
Other Details:
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Languages: eng Pagination: 978-84 Citation Subset: IM |
Affiliation:
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Institute of Molecular Hematology/Division of Hematology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan 410011, China. zgsllzy@public.cs.hn.cn |
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Calcium / metabolism* Caspase 3 Caspase 8 Caspases / genetics*, metabolism Cyclooxygenase Inhibitors / pharmacology Enzyme Activation Gene Expression Regulation, Enzymologic / drug effects* Humans Indomethacin / pharmacology* K562 Cells |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors; 53-86-1/Indomethacin; 7440-70-2/Calcium; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases |
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