Document Detail


2'-Epi-2'-O-acetylthevetin B induces apoptosis partly via Ca(2+)-mediated mitochondrial pathway in human hepatocellular carcinoma HepG2 cells.
MedLine Citation:
PMID:  19524689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
2'-Epi-2'-O-acetylthevetin B (GHSC-74), a cardiac glycoside, can be isolated from the seeds of Cerbera manghas L. We demonstrated that GHSC-74 reduced the viability of HepG2 cells in a time- and dose-dependent manner, and efficiently induced apoptosis without significantly decreasing the viability of Chang human liver cells and Swiss albino 3T3 fibroblasts, as indicated by annexin-V/PI binding assay and Hoechst 33342 staining. In addition, stimulation of HepG2 cells with GHSC-74 induced a series of intracellular events: (1) loss of mitochondrial membrane potential; (2) sustained elevation of cytosolic [Ca2+]; and (3) downregulation of Bcl-2. BAPTA-AM, a cytosolic Ca2+ chelator, partly suppressed cell death and prevented mitochondrial membrane potential from losing in GHSC-74-treated HepG2 cells. In contrast, EGTA, an extracellular Ca2+ chelator, exhibited a weaker effect as compared to that of BAPTA-AM. Taken together, the Ca(2+)-mediated mitochondrial pathway was found to be involved in GHSC-74-induced HepG2 cell apoptosis.
Authors:
Bo Feng; Cai-Guo Huang; Ruo-Hua Chen; Yue-Wei Guo; Bing-Hua Jiao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-12
Journal Detail:
Title:  Cell biology international     Volume:  33     ISSN:  1095-8355     ISO Abbreviation:  Cell Biol. Int.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-31     Completed Date:  2009-12-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307129     Medline TA:  Cell Biol Int     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  918-25     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
Anticarcinogenic Agents / chemistry,  pharmacology*
Apocynaceae / chemistry
Apoptosis*
Calcium / metabolism
Cardiac Glycosides / chemistry,  pharmacology*
Cell Line, Tumor
Chelating Agents / pharmacology
Egtazic Acid / analogs & derivatives,  pharmacology
Enzyme Inhibitors / chemistry,  pharmacology*
Fibroblasts / drug effects
Membrane Potential, Mitochondrial / drug effects,  physiology
Mice
Mitochondria / drug effects,  metabolism
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors,  metabolism*
Signal Transduction / drug effects,  physiology
Chemical
Reg. No./Substance:
0/2'-epi-2'-O-acetylthevetin B; 0/Anticarcinogenic Agents; 0/Cardiac Glycosides; 0/Chelating Agents; 0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 139890-68-9/1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; 67-42-5/Egtazic Acid; 7440-70-2/Calcium

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


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