Document Detail


Aloe emodin-induced apoptosis in t-HSC/Cl-6 cells involves a mitochondria-mediated pathway.
MedLine Citation:
PMID:  15910415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of our study was to clarify the apoptosis pathway induced by aloe emodin, an hydroxyanthraquinone present in aloe vera leaves, in rat hepatic stellate cells transformed by simian virus 40 (t-HSC/Cl-6), which retain the features of activated rat stellate cells. Apoptosis was determined by DNA fragmentation, caspase activity assay and western blotting analysis. Treatment of t-HSC/Cl-6 cells with 12.5, 25, or 50 microM aloe emodin inhibited t-HSC/Cl-6 cell viability in a dose- and time-dependent manner. The induction of apoptosis by aloe emodin was confirmed by typical DNA ladder formation and annexin v-propidium iodide flow-cytometric analysis. Aloe emodin treatment of t-HSC/Cl-6 cells caused activation of caspase-3 and caspase-9, detected with a caspase activity assay, although no change was observed in caspase-8 activity. Western blotting showed caspase-3 and caspase-9 active forms and the subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. Aloe emodin induced mitochondrial membrane depolarization. Our data also show that cytochrome c increased in the cytosol but decreased in the mitochondria in a time-dependent manner. Increased Bax and unchanged Bcl-2 levels resulted in an increased Bax/Bcl-2 ratio. Thus, our research provides evidence that aloe emodin-induced apoptosis involves a mitochondria-associated apoptosis pathway.
Authors:
Li-Hua Lian; Eun-Jeon Park; Hui-Shan Piao; Yu-Zhe Zhao; Dong Hwan Sohn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  96     ISSN:  1742-7835     ISO Abbreviation:  Basic Clin. Pharmacol. Toxicol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-24     Completed Date:  2005-09-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  495-502     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anthraquinones
Apoptosis*
Caspase 3
Caspase 9
Caspases / metabolism
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Cytochromes c / metabolism
DNA Fragmentation
Emodin / pharmacology*
Membrane Potentials / drug effects
Mitochondria / drug effects*,  metabolism,  physiology
Proto-Oncogene Proteins c-bcl-2 / metabolism
Rats
bcl-2-Associated X Protein
Chemical
Reg. No./Substance:
0/Anthraquinones; 0/Bax protein, rat; 0/Proto-Oncogene Proteins c-bcl-2; 0/aloe emodin; 0/bcl-2-Associated X Protein; 518-82-1/Emodin; 9007-43-6/Cytochromes c; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Casp9 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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


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