Trachootham Dunyaporn, Zhou Yan, Zhang Hui, Demizu Yusuke, Chen Zhao, Pelicano Helene, Chiao Paul J, Achanta Geetha, Arlinghaus Ralph B, Liu Jinsong, Huang Peng
Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Cell. 2006 Sep;10(3):241-52. doi: 10.1016/j.ccr.2006.08.009.
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.
活性氧（ROS）可刺激细胞增殖并诱导基因不稳定，癌细胞中ROS的增加通常被视为不良事件。在此，我们表明，利用β-苯乙基异硫氰酸酯（PEITC）可利用癌细胞中这种异常增加的ROS来选择性杀死癌细胞。用H-Ras（V12）对卵巢上皮细胞进行致癌转化或在造血细胞中表达Bcr-Abl会导致ROS生成增加，并使恶性细胞对PEITC高度敏感，PEITC可有效破坏谷胱甘肽抗氧化系统，并由于转化细胞活跃的ROS输出而导致ROS在这些细胞中优先大量积累。过量的ROS会导致线粒体氧化损伤、氧化还原敏感分子失活以及大量细胞死亡。在体内，PEITC具有治疗活性并能延长动物生存期。
