Document Detail


Eupafolin, a flavonoid isolated from Artemisia princeps, induced apoptosis in human cervical adenocarcinoma HeLa cells.
MedLine Citation:
PMID:  20397191     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although eupafolin, a flavone found in Artemisia princeps Pampanini, has been shown to inhibit the growth of several human cancer cells, its mode of action is poorly understood. In this study, we investigated the pro-apoptotic activities of eupafolin in human cervical carcinoma HeLa cells. It was found that eupafolin induced apoptosis in a dose-dependent manner, as evidenced by DNA fragmentation and the accumulation of positive cells for annexin V. In addition, eupafolin triggered the activations of caspases-3, -6, -7, -8, and -9 and the cleavages of their substrates, such as, poly (ADP-ribose) polymerase and lamin A/C. Furthermore, treatment with eupafolin resulted in a loss of mitochondrial membrane potential (DeltaPsi(m)), increased the release of cytochrome c to the cytosol, and altered the expression levels of B-cell lymphoma 2 (Bcl-2) family proteins. Interestingly, caspase-8, an initiator caspase, was activated after the loss of DeltaPsi(m) and the activations of caspases-3 and -9. Moreover, treatment with z-DEVD-fmk (a specific caspase-3 inhibitor) and the overexpression of Bcl-2 prevented eupafolin-stimulated caspase-8 activation. Altogether, these results suggest that the eupafolin-induced apoptosis in HeLa cells is mediated by caspase-dependent pathways, involving caspases-3, -9, and -8, which are initiated by the Bcl-2-dependent loss of DeltaPsi(m).
Authors:
Kyung-Sook Chung; Jung-Hye Choi; Nam-In Back; Myung-Sook Choi; Eun-Kyung Kang; Hae-Gon Chung; Tae-Sook Jeong; Kyung-Tae Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  54     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-08     Completed Date:  2011-01-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1318-28     Citation Subset:  IM    
Affiliation:
Department of Biomedical Science, College of Medical Science, Kyung-Hee University, Seoul, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / drug therapy*
Antineoplastic Agents, Phytogenic / chemistry,  isolation & purification,  pharmacology*
Apoptosis / drug effects*
Artemisia / chemistry*
Caspases / metabolism
Cell Line, Tumor
DNA Fragmentation / drug effects
Down-Regulation / drug effects
Enzyme Activation / drug effects
Female
Flavones / chemistry,  isolation & purification,  pharmacology*
Hela Cells
Humans
Inhibitory Concentration 50
Kinetics
Membrane Potential, Mitochondrial / drug effects
Mitochondria / drug effects,  enzymology
Permeability / drug effects
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism
Uterine Cervical Neoplasms / drug therapy*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Flavones; 0/Proto-Oncogene Proteins c-bcl-2; 0/eupafolin; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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