Neoplasma. 2017;64(2):192-198. doi: 10.4149/neo_2017_204.
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.
草酰乙酸 (OA) 是三羧酸循环的中间产物之一。除了在能量产生中的作用外，OA 可能对细胞还有其他影响。我们在此报告，OA 通过诱导细胞凋亡和活性氧 (ROS) 积累，对人肝癌细胞系 HepG2 具有依赖细胞类型的细胞毒性作用。在我们的研究中，OA 降低了 HepG2 细胞的活力和集落形成能力，并诱导细胞死亡。OA 处理的 HepG2 细胞中 caspase-3 活性增加，促凋亡蛋白 Bax 上调，抗凋亡蛋白 Bcl-2 下调，表明细胞凋亡通过内在途径参与细胞死亡。OA 处理的 HepG2 细胞中的 ROS 水平增加。抗氧化剂 N-乙酰半胱氨酸 (NAC) 和谷胱甘肽 (GSH) 可预防 OA 诱导的细胞减少，但不会改变增强的凋亡 Bax/Bcl-2 mRNA 比值。这些结果表明，OA 诱导的 HepG2 细胞凋亡不是由氧化损伤驱动的，至少有两种不同的机制导致 OA 对 HepG2 细胞的细胞毒性作用，一种机制通过 ROS 介导，另一种涉及凋亡。这些研究扩展了 OA 的生物学功能谱，并为肝细胞癌可能被 OA 靶向提供了一种机制。
