Hexokinase type II (HK II) is the key enzyme for maintaining increased glycolysis in cancer cells where it is overexpressed. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, induces cell death in cancer cells. To elucidate the molecular mechanism of 3-BrPA-induced cell death, we used the hepatoma cell lines SNU449 (low expression of HKII) and Hep3B (high expression of HKII). 3-BrPA induced ATP depletion-dependent necrosis and apoptosis in both cell lines. 3-BrPA increased intracellular reactive oxygen species (ROS) leading to mitochondrial dysregulation. NAC (N-acetyl-L: -cysteine), an antioxidant, blocked 3-BrPA-induced ROS production, loss of mitochondrial membrane potential and cell death. 3-BrPA-mediated oxidative stress not only activated poly-ADP-ribose (PAR) but also translocated AIF from the mitochondria to the nucleus. Taken together, 3-BrPA induced ATP depletion-dependent necrosis and apoptosis and mitochondrial dysregulation due to ROS production are involved in 3-BrPA-induced cell death in hepatoma cells.

中文翻译：

---

活性氧介导的线粒体失调在 3-溴丙酮酸诱导的肝癌细胞细胞死亡中的作用：ROS 介导的 3-BrPA 细胞死亡。

己糖激酶 II 型 (HK II) 是维持癌细胞中糖酵解增加的关键酶，其中过表达。3-溴丙酮酸 (3-BrPA) 是 HK II 的抑制剂，可诱导癌细胞死亡。为了阐明 3-BrPA 诱导细胞死亡的分子机制，我们使用肝癌细胞系 SNU449（HKII 低表达）和 Hep3B（HKII 高表达）。3-BrPA 在两种细胞系中诱导 ATP 消耗依赖性坏死和细胞凋亡。3-BrPA 增加细胞内活性氧 (ROS)，导致线粒体失调。NAC（N-乙酰-L：-半胱氨酸）是一种抗氧化剂，可阻止 3-BrPA 诱导的 ROS 产生、线粒体膜电位丧失和细胞死亡。3-BrPA 介导的氧化应激不仅激活了聚 ADP 核糖 (PAR)，而且还将 AIF 从线粒体转移到细胞核。综合起来，