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As2O3 induces apoptosis in human hepatocellular carcinoma HepG2 cells through a ROS-mediated mitochondrial pathway and activation of caspases

机译:As2O3通过ROS介导的线粒体途径和胱天蛋白酶的活化诱导人肝癌HepG2细胞凋亡

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摘要

Arsenic trioxide (As2O3) has been shown to induce apoptosis in hepatocellular carcinoma cells. However, the molecular mechanism of As2O3-induced apoptosis in the hepatocellular carcinoma cells remains poorly understood. Here, we investigated the impact of As2O3 exposure on the human hepatocellular carcinoma cell line HepG2 and examined the underlying mechanism of cell death. As2O3 induced apoptosis of HepG2 cells in a dose- and time-dependent manner and caused a massive production of reactive oxygen species (ROS). The antioxidant N-acetylcysteine (NAC) was able to prevent As2O3-induced cell death, implying an involvement of ROS in the induction of As2O3-triggered apoptosis. Furthermore, As2O3 initiated apoptosis by triggering of the mitochondria apoptotic pathway as indicated by inhibited Bcl-2 expression, a collapse of the mitochondrial membrane potential (MMP), release of cytochrome c and activation of the caspase cascade. However, these As2O3-induced events can be prevented by NAC. Taken together, these findings suggest that the As2O3 induced apoptosis through a ROS-mediated mitochondrial pathway and activation of caspases.
机译:三氧化二砷(As2O3)已被证明可诱导肝细胞癌细胞凋亡。但是,尚不清楚As2O3诱导肝癌细胞凋亡的分子机制。在这里,我们调查了As2O3暴露对人肝癌细胞系HepG2的影响,并研究了细胞死亡的潜在机制。 As2O3以剂量和时间依赖性方式诱导HepG2细胞凋亡,并导致大量产生活性氧(ROS)。抗氧化剂N-乙酰半胱氨酸(NAC)能够防止As2O3诱导的细胞死亡,这表明ROS参与了As2O3触发的细胞凋亡的诱导。此外,As2O3通过触发线粒体凋亡途径来启动细胞凋亡,如抑制的Bcl-2表达,线粒体膜电位(MMP)崩溃,细胞色素c的释放和胱天蛋白酶级联反应的激活所表明的。但是,NAC可以防止这些As2O3诱导的事件。综上所述,这些发现表明As 2 O 3 通过ROS介导的线粒体途径和胱天蛋白酶的激活诱导细胞凋亡。

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