Document Detail

Induction of apoptosis by esculetin in human leukemia cells.
MedLine Citation:
PMID:  11282109     Owner:  NLM     Status:  MEDLINE    
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.
C Y Chu; Y Y Tsai; C J Wang; W L Lin; T H Tseng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  416     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-04-03     Completed Date:  2001-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  25-32     Citation Subset:  IM    
Department and Institute of Biochemistry, Chung Shan Medical and Dental College, No. 110, Section 1, Chien Kuo N. Road, 402, Taichung, Taiwan.
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MeSH Terms
Antioxidants / 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
Poly(ADP-ribose) Polymerases / drug effects,  metabolism
Proto-Oncogene Proteins c-bcl-2 / drug effects,  metabolism
Time Factors
Umbelliferones / pharmacology*
Reg. No./Substance:
0/Antioxidants; 0/Cytochrome c Group; 0/Proto-Oncogene Proteins c-bcl-2; 0/Umbelliferones; 305-01-1/esculetin; EC Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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