Document Detail

Induction of apoptosis in HeLa cells by 3beta-hydroxyurs-12-en-27-oic acid.
MedLine Citation:
PMID:  17193306     Owner:  NLM     Status:  MEDLINE    
3Beta-hydroxyurs-12-en-27-oic acid (1), a pentacyclic triterpenoid isolated from the rhizomes of Astilbe chinensis, was structurally very similar to ursolic acid, with the only difference being the interchange of the COOH and Me group at C(14) and C(17). Ursane-type triterpene with a COOH group at C(14) is present in a limited number of natural resources. Compound 1 was found to exhibit more distinctive cytotoxicity toward human cervical squamous carcinoma (HeLa) cells than ursolic acid, suggesting that the position of the COOH group significantly affects the cytotoxicity of ursane-type pentacyclic triterpenes with a COOH group. To elucidate the underlying biological mechanism responsible for the cytotoxicity of 1, we investigated its growth-inhibitory and apoptosis-inducing effect on HeLa cells. Compound 1 induced a marked concentration- and time-dependent inhibition of cell proliferation with an IC50 value of 6.80+/-0.88 microg/ml following 48 h incubation. The drug-treated HeLa cells displayed typical morphological apoptotic characteristics and formation of DNA ladders in agarose-gel electrophoresis. Flow cytometric analysis showed that the cell cycle was arrested in G0/G1 phase by 1, and the apoptotic rate of HeLa cells treated for 48 h with 20 microg/ml of 1 was 21.08+/-2.14%. Also, 1 increased and decreased the expression of Bax and Bcl-2 proteins, respectively, and lowered the mitochondrial transmembrane potential (delta psi(m)). The peptidic caspase-3 inhibitor DEVD-CHO (NH2-Asp-Glu-Val-Asp-CHO, at 2 microM) could increase the viability of HeLa cells previously treated with 1. These results indicate that 1 induces efficient cell apoptosis through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering delta psi(m), and by activating the caspase-3 pathway.
Quan-Fang Zheng; Hong-Xiang Sun; Qiao-Jun He; Yi-Ping Ye
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemistry & biodiversity     Volume:  3     ISSN:  1612-1880     ISO Abbreviation:  Chem. Biodivers.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-12-28     Completed Date:  2007-03-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197449     Medline TA:  Chem Biodivers     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  742-53     Citation Subset:  IM    
College of Animal Sciences, Zhejiang University, Hangzhou 310029, PR China.
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MeSH Terms
Apoptosis / drug effects*
Caspase 3 / antagonists & inhibitors,  metabolism
Cell Shape
DNA Fragmentation / drug effects
Enzyme Inhibitors / pharmacology
Hela Cells
Membrane Potentials / drug effects
Microscopy, Electron, Transmission
Mitochondrial Membranes / drug effects
Molecular Structure
Proto-Oncogene Proteins c-bcl-2 / metabolism
Triterpenes / chemistry,  pharmacology*
Reg. No./Substance:
0/3-hydroxyurs-12-en-27-oic acid; 0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/Triterpenes; EC 3.4.22.-/Caspase 3

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