Abstract |
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 | C Y Chu, Y Y Tsai, C J Wang, W L Lin, T H Tseng |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 416
Issue 1-2
Pg. 25-32
(Mar 23 2001)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 11282109
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antioxidants
- Cytochrome c Group
- Proto-Oncogene Proteins c-bcl-2
- Umbelliferones
- Poly(ADP-ribose) Polymerases
- CASP3 protein, human
- Caspase 3
- Caspases
- esculetin
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Topics |
- 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)
- Humans
- Poly(ADP-ribose) Polymerases
(drug effects, metabolism)
- Proto-Oncogene Proteins c-bcl-2
(drug effects, metabolism)
- Time Factors
- Umbelliferones
(pharmacology)
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