Octyl gallate (OG) is an antioxidant that has shown anti-tumor, anti-diabetic and anti-amyloidogenic activities. Mitochondria play an important role in hepatocellular carcinoma, mainly by maintaining accelerated cellular proliferation through the production of ATP. Thus, the mitochondria may be a target for antitumor therapies. Here, we investigated the effects of OG in the hepatocarcinoma cell line (HepG2) and the mechanisms involved. We report, for the first time, that treatment with OG for 24h inhibited HepG2 cell growth by decreasing mitochondrial activity and mass, which led to the reduction of ATP levels. This reduction in the energy supply triggered a decrease in Ki67 protein expression, leading cells to cycle arrest. In addition, treatment with two doses of OG for 48h induced loss of mitochondrial functionality, mitochondrial swelling and apoptosis. Finally, we report that HepG2 cells had no resistance to treatment after multiple doses. Collectively, our findings indicate that metabolic dysregulation and Ki67 protein reduction are key events in the initial anti-proliferative action of OG, whereas mitochondrial swelling and apoptosis induction are involved in the action mechanism of OG after prolonged exposure. This suggests that OG targets mitochondria, thus representing a candidate for further research on therapies for hepatocarcinoma.

中文翻译：

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没食子酸辛酯降低ATP水平和Ki67表达，导致HepG2细胞停止细胞周期并在线粒体介导的细胞凋亡。

没食子酸辛酯（OG）是一种抗氧化剂，具有抗肿瘤，抗糖尿病和抗淀粉样变性的活性。线粒体在肝细胞癌中起重要作用，主要是通过产生ATP来维持加速的细胞增殖。因此，线粒体可能是抗肿瘤治疗的目标。在这里，我们研究了OG在肝癌细胞系（HepG2）中的作用及其机制。我们首次报道，OG处理24h通过降低线粒体活性和质量抑制了HepG2细胞的生长，从而降低了ATP的水平。能量供应的减少触发了Ki67蛋白表达的下降，导致细胞停滞。此外，用两剂OG治疗48h会导致线粒体功能丧失，线粒体肿胀和凋亡。最后，我们报道了多次给药后，HepG2细胞对治疗没有抵抗力。总的来说，我们的研究结果表明，代谢异常和Ki67蛋白的减少是OG初始抗增殖作用中的关键事件，而线粒体肿胀和细胞凋亡诱导则是长时间暴露后OG的作用机制。这表明OG靶向线粒体，因此代表着肝癌治疗方法的进一步研究的候选人。线粒体肿胀和凋亡诱导与OG长时间暴露后的作用机制有关。这表明OG靶向线粒体，因此代表着肝癌治疗方法的进一步研究的候选人。线粒体肿胀和凋亡诱导与OG长时间暴露后的作用机制有关。这表明OG靶向线粒体，因此代表着肝癌治疗方法的进一步研究的候选人。