title: Cytotoxic effect of oxaloacetate on HepG2-human hepatic carcinoma cells via apoptosis and ROS accumulation.
abstract: Oxaloacetate (OA) is one of the intermediates of the Krebs cycle. In addition to its role in energy production, OA may have other effects on the cell. We report here that OA could have a cell type dependent cytotoxic effect on the human hepatic carcinoma cell line HepG2 through induction of apoptosis and reactive oxygen species (ROS) accumulation. In our study, OA decreased the viability and colony formation of HepG2 cells and induced cell death. Caspase-3 activity was increased, the pro-apoptotic protein Bax was up-regulated, and the anti-apoptotic protein Bcl-2 was down-regulated in OA-treated HepG2 cells indicating that apoptosis through the intrinsic pathway was involved in the cell death. The ROS level in OA-treated HepG2 cells was increased. The anti-oxidant N-acetylcysteine (NAC) and glutathione (GSH) prevented the OA-induced decrease in cell but did not alter the enhanced apoptotic Bax/Bcl-2 mRNA ratio. These results suggest that the OA-induced apoptosis of HepG2 cell is not driven by oxidative damage and at least two distinct mechanisms, one mediated by ROS and one involving apoptosis, result in the cytotoxic effects of OA on HepG2 cells. These studies expand the biological functional repertoire of OA and provide a mechanism by which hepatocellular carcinoma may be targeted by OA.
authors.forename: Y
authors.initials: Y
authors.lastname: Jiao
authors.forename: L
authors.initials: L
authors.lastname: Ji
authors.forename: Y
authors.initials: Y
authors.lastname: Kuang
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000111:Acetylcysteine; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D005978:Glutathione; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D062907:Oxaloacetic Acid / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D062907:Oxaloacetic Acid; C505407:CASP3 protein, human; D053148:Caspase 3; D005978:Glutathione; D000111:Acetylcysteine
keywords: HepG2 cells; apoptosis reactive oxygen species.; oxaloacetate