Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate
Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate
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DOI：
10.1016/j.ccr.2006.08.009
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发表时间：
2006-09-01
期刊：
影响因子：
50.3
通讯作者：
Huang, Peng
中科院分区：
文献类型：
--
作者：
Trachootham, Dunyaporn;Zhou, Yan;Huang, Peng
活性氧簇(ROS)刺激细胞增殖和诱导遗传不稳定，它们在癌细胞中的增加通常被视为一种不良事件。在这里，我们展示了这种ROS的异常增加可以被利用来使用β-苯乙基异硫氰酸酯(PEITC)选择性地杀死癌细胞。卵巢上皮细胞与H-RAS(V12)或bcr-Abl在造血细胞中表达的致癌转化导致ROS生成增加，并使恶性细胞对PEITC高度敏感，这有效地禁用了谷胱甘肽抗氧化系统，并由于其活跃的ROS输出而导致转化细胞优先积累严重的ROS。过量的ROS会导致线粒体氧化损伤、氧化还原敏感分子失活和大量细胞死亡。在体内，PEITC具有治疗活性和延长动物存活的作用。
Reactive oxygen species (ROS) stimulate cell proliferation and induce genetic instability, and their increase in cancer cells is often viewed as an adverse event. Here, we show that such abnormal increases in ROS can be exploited to selectively kill cancer cells using beta-phenylethyl isothiocyanate (PEITC). Oncogenic transformation of ovarian epithelial cells with H-Ras(V12) or expression of Bcr-Abl in hematopoietic cells causes elevated ROS generation and renders the malignant cells highly sensitive to PEITC, which effectively disables the glutathione antioxidant system and causes severe ROS accumulation preferentially in the transformed cells due to their active ROS output. Excessive ROS causes oxidative mitochondrial damage, inactivation of redox-sensitive molecules, and massive cell death. In vivo, PEITC exhibits therapeutic activity and prolongs animal survival.