Cytotoxic effect of oxaloacetate on HepG2-human hepatic carcinoma cells via apoptosis and ROS accumulation
Cytotoxic effect of oxaloacetate on HepG2-human hepatic carcinoma cells via apoptosis and ROS accumulation
复制标题
草酰乙酸通过凋亡和ROS积累对HepG2-人肝癌细胞的细胞毒作用
DOI：
10.4149/neo_2017_204
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发表时间：
2017-01-01
期刊：
影响因子：
3
通讯作者：
Yang, Q.
中科院分区：
文献类型：
--
作者：
Jiao, Y.;Ji, L.;Yang, Q.
草酰乙酸酯(OA)是克雷布斯循环的中间体之一。除了在能量生产中的作用外，OA还可能对细胞有其他影响。我们在此报道了OA对人肝癌细胞株HepG2具有细胞类型依赖性的细胞毒作用，其机制可能是通过诱导细胞凋亡和ROS积聚来实现的。在我们的研究中，OA降低了HepG2细胞的存活率和集落形成，并诱导了细胞死亡。经OA处理的HepG2细胞caspase-3活性升高，促凋亡蛋白Bax表达上调，抗凋亡蛋白Bcl2表达下调，提示细胞通过内源性途径参与了细胞死亡。OA处理后的HepG2细胞内ROS水平升高。抗氧化剂N-乙酰半胱氨酸(NAC)和谷胱甘肽(GSH)可阻止OA诱导的细胞减少，但不改变Bax/Bcl2 m RNA比值的升高。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，一种是由ROS介导的，另一种是涉及细胞凋亡的，导致了OA对HepG2细胞的细胞毒作用。这些研究扩展了骨关节炎的生物学功能，并提供了一种肝细胞癌可能成为骨关节炎靶点的机制。
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.