| Induction of apoptosis by esculetin in human leukemia cells. | |
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MedLine Citation:
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PMID: 11282109 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Esculetin, a coumarin compound, has been shown to exhibit antioxidant and anti-inflammatory effects. In the present study, esculetin was found to inhibit the survival of human promyelocytic leukemia HL-60 cells in a concentration-dependent and time-dependent manner. HL-60 cells underwent internucleosomal DNA fragmentation and morphological changes characteristic of apoptosis after a 24-h treatment with esculetin (100 microM). Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 40.93% after a 36-h treatment with esculetin (100 microM). Further investigation showed that esculetin induced the release of cytochrome c from mitochondria into cytosol in a time-dependent and concentration-dependent manner. Moreover, esculetin application reduced Bcl-2 protein expression to 58% after 9 h as compared with that time at 0. Cysteine protease 32 kDa proenzyme (CPP32), a caspase 3, was activated and its substrate, poly (adenosine diphosphate-ribose) polymerase, was cleaved after a 24-h treatment of HL-60 cells with esculetin. These data suggest that esculetin induces apoptosis in human leukemia cells by increasing cytosolic translocation of cytochrome c and activation of CPP32. |
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Authors:
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C Y Chu; Y Y Tsai; C J Wang; W L Lin; T H Tseng |
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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: European journal of pharmacology Volume: 416 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2001 Mar |
Date Detail:
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Created Date: 2001-04-03 Completed Date: 2001-07-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 25-32 Citation Subset: IM |
Affiliation:
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Department and Institute of Biochemistry, Chung Shan Medical and Dental College, No. 110, Section 1, Chien Kuo N. Road, 402, Taichung, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antioxidants
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pharmacology* Apoptosis / drug effects* Caspase 3 Caspases / drug effects, metabolism Cell Survival / drug effects Cytochrome c Group / drug effects, metabolism DNA Fragmentation / drug effects Dose-Response Relationship, Drug HL-60 Cells / cytology, drug effects, metabolism Humans Poly(ADP-ribose) Polymerases / drug effects, metabolism Proto-Oncogene Proteins c-bcl-2 / drug effects, metabolism Time Factors Umbelliferones / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Cytochrome c Group; 0/Proto-Oncogene Proteins c-bcl-2; 0/Umbelliferones; 305-01-1/esculetin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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