trans-10-cis-12-conjugated-linoleic-acid and Liver-Neoplasms

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.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; BH3 Interacting Domain Death Agonist Protein; Carcinoma, Hepatocellular; Carrier Proteins; Caspase 3; Caspase 9; Caspases; Cell Line, Tumor; Enzyme Activation; Kinetics; Linoleic Acids, Conjugated; Liver Neoplasms; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Rats