Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
Oncol Rep. 2011 Mar;25(3):871-7. doi: 10.3892/or.2010.1121. Epub 2010 Dec 24.
Propyl gallate (PG) used in processed food and medicinal preparations has been shown to induce cell death in normal and cancer cells. The inhibition of proteasome function has emerged as a useful strategy to maneuver apoptosis. Here, we investigated the combined effects of PG and MG132 (a proteasome inhibitor) on HeLa cells in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH). PG induced growth inhibition and apoptosis in HeLa cells, accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨm), activation of caspase 3 and PARP cleavage. The levels of ROS and GSH depletion were increased in PG-treated HeLa cells. MG132 intensified apoptosis and PARP cleavage in PG-treated HeLa cells. MG132 also increased ROS levels including mitochondrial O2•-, MMP (ΔΨm) loss and GSH depletion in PG-treated HeLa cells. PG induced a G1 phase arrest of the cell cycle in HeLa cells, which was significantly prevented by MG132. MG132 alone inhibited HeLa cell growth via inducing the cell cycle arrests and triggering apoptosis. Conclusively, the inhibition of proteasome by MG132 plays a role as an enhancement factor in PG-induced apoptosis of HeLa cells via increasing ROS levels and GSH depletion.
没食子酸丙酯（PG）在加工食品和药物制剂中被证明可诱导正常和癌细胞死亡。抑制蛋白酶体功能已成为一种诱导细胞凋亡的有用策略。在这里，我们研究了 PG 和 MG132（一种蛋白酶体抑制剂）联合作用对 HeLa 细胞生长、细胞死亡、活性氧（ROS）和谷胱甘肽（GSH）的影响。PG 诱导 HeLa 细胞生长抑制和凋亡，伴随着线粒体膜电位（MMP；ΔΨm）丧失、caspase 3 激活和 PARP 切割。PG 处理的 HeLa 细胞中 ROS 和 GSH 耗竭水平增加。MG132 增强了 PG 处理的 HeLa 细胞中的凋亡和 PARP 切割。MG132 还增加了 PG 处理的 HeLa 细胞中的 ROS 水平，包括线粒体 O2•-、MMP（ΔΨm）丧失和 GSH 耗竭。PG 诱导 HeLa 细胞细胞周期停滞在 G1 期，这被 MG132 显著阻止。MG132 单独通过诱导细胞周期停滞和触发凋亡抑制 HeLa 细胞生长。综上所述，MG132 抑制蛋白酶体通过增加 ROS 水平和 GSH 耗竭在 PG 诱导的 HeLa 细胞凋亡中发挥增强因子的作用。
