【摘 要】
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Aim Oxaloacetate (OA) is one of the intermediates in the Krebs cycle.In addition to its role in the metabolism of energy production, OA may have other effects on the cell.We report in the present stud
【机 构】
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Department of Pathogenobiology,College of Basic Medical Sciences,Jilin University,Changchun Jilin 13
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Aim Oxaloacetate (OA) is one of the intermediates in the Krebs cycle.In addition to its role in the metabolism of energy production, OA may have other effects on the cell.We report in the present study that OA could have a cell type dependent cytotoxic effect on the human hepatic carcinoma cell line HepG2 through induction of apoptosis and ROS accumulation.In our study, OA decreased the viability and colony formation of HepG2 cell and induced cell death.Caspase3 activity was increased, proapoptotic protein Bax was upregulated, and antiapoptotic protein Bcl2 was downregulated in OAtreated HepG2 cells indicating that apoptosis through the intrinsic pathway was involved in the death of the cell.The level of reactive oxygen species (ROS) in OAtreated HepG2cells was increased.Antioxidant Nacetylcysteine (NAC) and glutathione (GSH) prevented the viability of the cell induced by OA from decrease but could not alleviate the enhanced level of apoptotic Bax/Bcl2 mRNA expression ratio, which suggests that the OAinduced apoptosis of HepG2 cell is not driven by oxidative damage and at least two distinct mechanisms, one mediated by ROS and one involving apoptosis, lead to the cytotoxic effect 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 to kill the cancer cells.
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