Document Detail

Aesculetin-induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway in human cervical cancer cells.
MedLine Citation:
PMID:  20390763     Owner:  NLM     Status:  MEDLINE    
Aesculetin (1) is an important coumarin found in various plant materials. It has been shown to have antiproliferative effects on several types of human cancer cells, but its effect on cervical cancer cells in vitro is unknown. In this study, we investigated that the cytotoxic effect of 1 on a non-cancer cell line (293) was smaller than on a tumor cell line (HeLa). This is the first report showing the possible mechanism of antiproliferative effect of 1 for the prevention of cervical cancer in cell culture models. It was found that 1 inhibited cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies, generation of reactive oxygen species (ROS), and the accumulation of cells in the sub-G1 phase. Treatment with compound 1 decreased the cell growth in a dose-dependent manner with an IC(50) value of 37.8 microM. Aesculetin-induced apoptosis was correlated with mitochondrial dysfunction (DeltaPsi(m)), leading to the release of cytochrome c from the mitochondria to the cytosol, as well as the proteolytic activation of caspases in HeLa cells. These results indicate that 1 induces apoptosis in HeLa cells through a ROS-mediated mitochondrial dysfunction pathway.
Jin Yang; Yu-Ling Xiao; Xian-Ran He; Guo-Fu Qiu; Xian-Ming Hu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of Asian natural products research     Volume:  12     ISSN:  1477-2213     ISO Abbreviation:  J Asian Nat Prod Res     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-05-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888334     Medline TA:  J Asian Nat Prod Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  185-93     Citation Subset:  IM    
State Key Laboratory of Virology, College of Pharmacy, Wuhan University, Wuhan, China.
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MeSH Terms
Antineoplastic Agents, Phytogenic / chemistry,  pharmacology*
Apoptosis / drug effects*
Bisbenzimidazole / diagnostic use
Caspases / drug effects,  metabolism
Cytochromes c / metabolism
Drug Screening Assays, Antitumor
Hela Cells
Mitochondria / drug effects*,  enzymology,  physiology
Models, Biological
Molecular Structure
Plants, Medicinal / chemistry
Tumor Cells, Cultured
Umbelliferones / chemistry,  pharmacology*
Uterine Cervical Neoplasms
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Umbelliferones; 23491-44-3/Bisbenzimidazole; 305-01-1/esculetin; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

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