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 cou...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 cytoto^ic 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. Caspase-3 activity was increased, pro-apoptotic protein Bax was up-regulated, and anti-ap- optotic protein Bcl-2 was clown-regulated in OA-treated 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 OA-treated HepG2 cells was increased. Anti-oxidant N-acetylcysteine （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/Bcl-2 mRNA expres- sion ratio, which suggests 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, 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.展开更多
文摘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 cytoto^ic 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. Caspase-3 activity was increased, pro-apoptotic protein Bax was up-regulated, and anti-ap- optotic protein Bcl-2 was clown-regulated in OA-treated 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 OA-treated HepG2 cells was increased. Anti-oxidant N-acetylcysteine （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/Bcl-2 mRNA expres- sion ratio, which suggests 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, 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.
