Document Detail


Trans10, cis12-conjugated linoleic acid induces mitochondria-related apoptosis and lysosomal destabilization in rat hepatoma cells.
MedLine Citation:
PMID:  16005259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Conjugated linoleic acid (CLA) is a powerful anti-carcinogenic fatty acid. Previously, we showed that 10trans 12cis (10t, 12c) CLA induced apoptotic cell death in rat hepatoma. Here, we demonstrated significant cytotoxic effects of 1 muM 10t, 12c-CLA, but not 9c, 11t-CLA, on dRLh-84 rat hepatoma cells. 9t, 11t and 9c, 11c-CLA also showed low levels of cytotoxic activity. 10t, 12c-CLA activated caspase-3, 9 followed by cytochrome c release from mitochondria into the cytosol. Inhibitors of caspase-3, 9 blocked the cytotoxicity of 10t, 12c-CLA. 10t, 12c-CLA also induced translocation of Bax protein into the mitochondrial membrane and cleavage of Bid protein. Lysosomal destabilization induced by 10t, 12c-CLA was observed by monitoring the re-localization of Acridine Orange and the leakage of beta-hexosaminidase from lysosomes. 10t, 12c-CLA directly degraded the isolated lysosomes from the rat liver. Our observations indicate that 10t, 12c-CLA induces mitochondria-related apoptosis accompanied by lysosomal destabilization in rat hepatoma cells.
Authors:
Masao Yamasaki; Yumi Miyamoto; Hitomi Chujo; Kazuo Nishiyama; Hirofumi Tachibana; Koji Yamada
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1735     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-15     Completed Date:  2005-10-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  176-84     Citation Subset:  IM    
Affiliation:
Division of Food Science and Nutrition, Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, Miyazaki University, Miyazaki 889-2192, Japan. myamasaki@cc.miyazaki-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
BH3 Interacting Domain Death Agonist Protein
Carcinoma, Hepatocellular
Carrier Proteins / metabolism
Caspase 3
Caspase 9
Caspases / metabolism
Cell Line, Tumor
Enzyme Activation
Kinetics
Linoleic Acids, Conjugated / pharmacology*
Liver Neoplasms
Mitochondria / drug effects,  physiology*
Proto-Oncogene Proteins c-bcl-2 / metabolism
Rats
bcl-2-Associated X Protein
Chemical
Reg. No./Substance:
0/BH3 Interacting Domain Death Agonist Protein; 0/Bax protein, rat; 0/Bid protein, rat; 0/Carrier Proteins; 0/Linoleic Acids, Conjugated; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 0/trans-10,cis-12-conjugated linoleic acid; 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

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