Document Detail

The apoptotic effect of brucine from the seed of Strychnos nux-vomica on human hepatoma cells is mediated via Bcl-2 and Ca2+ involved mitochondrial pathway.
MedLine Citation:
PMID:  16443926     Owner:  NLM     Status:  MEDLINE    
In an attempt to dissect the mechanism of Strychnos nux-vomica, a commonly used Chinese folk medicine in the therapy of liver cancer, the cytotoxic effects of four alkaloids in Strychnos nux-vomica, brucine, brucine N-oxide, strychnine, and isostrychnine, on human hepatoma cells (HepG2) were screened by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrasolium bromide (MTT) assay. Brucine, among the four alkaloids, exhibited the strongest toxic effect, the mechanism of which was found to cause HepG2 cell apoptosis, since brucine caused HepG2 cell shrinkage, the formation of apoptotic bodies, DNA fragmentation, cell cycle arrest, as well as phosphatidylserine externalization, all of which are typical characteristics of apoptotic programmed cell death. Brucine-induced HepG2 cell apoptosis was caspase dependent, with caspase-3 activated by caspase-9. Brucine also caused the proteolytic processing of caspase-9. In addition, brucine caused depolarization of the mitochondrial membrane of HepG2 cells, the inhibition of which by cyclosporine A completely abrogated the activation of casapses and release of cytochrome c in brucine-treated HepG2 cells. These findings suggested a pivotal role of mitochondrial membrane depolarization in HepG2 cell apoptosis elicited by brucine. Furthermore, brucine induced a rapid and sustained elevation of intracellular [Ca2+], which compromised the mitochondrial membrane potential and triggered the process of HepG2 cell apoptosis. Finally, Bcl-2 was found to predominately control the whole event of cell apoptosis induced by brucine. The elevation of [Ca2+]i caused by brucine was also suppressed by overexpression of Bcl-2 protein in HepG2 cells. From the facts given above, Ca2+ and Bcl-2 mediated mitochondrial pathway were found to be involved in brucine-induced HepG2 cell apoptosis.
Xukun Deng; Fangzhou Yin; Xiaoyu Lu; Baochang Cai; Wu Yin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-27
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  91     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-10     Completed Date:  2006-06-21     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  59-69     Citation Subset:  IM    
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China, 210029.
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MeSH Terms
Apoptosis / drug effects*
Calcium / metabolism*
Carcinoma, Hepatocellular / enzymology,  metabolism,  pathology*
Caspase 3
Caspases / metabolism
Cell Line, Tumor
Cyclic N-Oxides / pharmacology
Cytochromes c / metabolism
Enzyme Activation
Liver Neoplasms / enzymology,  metabolism,  pathology*
Mitochondria, Liver / drug effects*,  metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Seeds / chemistry*
Strychnine / analogs & derivatives*,  isolation & purification,  pharmacology
Strychnos nux-vomica / embryology*
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Proto-Oncogene Proteins c-bcl-2; 17301-81-4/brucine N-oxide; 357-57-3/brucine; 57-24-9/Strychnine; 7440-70-2/Calcium; 9007-43-6/Cytochromes c; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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

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