Cytotoxic effect of peroxisome proliferator fenofibrate on human HepG2 hepatoma cell line and relevant mechanisms
Cytotoxic effect of peroxisome proliferator fenofibrate on human HepG2 hepatoma cell line and relevant mechanisms
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DOI：
10.1006/taap.2002.9538
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发表时间：
2002-12-15
影响因子：
3.8
通讯作者：
Zhao, BL
中科院分区：
文献类型：
--
作者：
Jiao, HL;Zhao, BL
本工作的目的是研究降血脂剂非诺贝特（FF），过氧化物酶体增殖剂（PP），对人肝癌细胞HepG2的影响，并表征所涉及的细胞内事件。结果显示，与啮齿动物中的促肿瘤作用相反，高浓度FF通过涉及活性氧（ROS）水平增加和细胞内GSH耗尽的机制诱导人HepG2细胞死亡，这通过线粒体功能障碍和细胞内Ca2+稳态扰动导致细胞死亡。FF处理后表达核受体过氧化物酶体增殖物激活受体α（PPARalpha）。结果表明，尽管长期给予PP会导致易感物种（例如，FF以剂量相关的方式抑制人HepG2细胞的生长，并且氧化应激参与了这种作用。(C)2002年爱思唯尔科学（美国）。
The aim of this work was to investigate the effects of hypolipidemic agent fenofibrate (FF), a peroxisome proliferator (PP), on human HepG2 cells and to characterize the intracellular events involved. The results showed that, in contrast to the tumor-promoting effects in rodents, high FF concentrations induced human HepG2 cell death through a mechanism involving an increase in the levels of reactive oxygen species (ROS) and intracellular GSH depletion, which led, through mitochondrial dysfunction and perturbation of intracellular Ca2+ homeostasis, to cell death. The nuclear receptor peroxisome proliferator-activated receptor-alpha (PPARalpha) was expressed following FF treatment. The results suggest that, although long-term administration of PPs causes liver cancer in susceptible species (e.g., rodents), FF inhibits the growth of human HepG2 cells in a dose-related manner and oxidative stress was involved in this effect. (C) 2002 Elsevier Science (USA).