Yoo Dong Ryeol, Jang Yun Ho, Jeon Yeong Keul, Kim Ju Yeon, Jeon Won, Choi Yeon Joo, Nam Myeong Jin
Department of Biological Science, Gachon University of Medicine and Science, Yeonsu-dong, Yeonsu-gu, Incheon, Republic of Korea.
Cancer Lett. 2009 Sep 8;282(1):48-54. doi: 10.1016/j.canlet.2009.02.051. Epub 2009 Apr 1.
Luteolin has been shown to exhibit anti-cancer activity against several forms of cancers, including human hepatic cancers. Many in vitro studies have reported anti-oxidant effects of luteolin. Here, we demonstrate using ROS (reactive oxygen species) detection in the human hepatocellular carcinoma cell line, Huh-7, that anti-cancer action of luteolin are mediated through an increasing in intracellular ROS levels. To identify proteins potentially involved in this mechanism, a two-dimensional electrophoresis (2-DE)-based-proteomic approach was employed. Proteomic analysis revealed that several proteins were associated with the anti-cancer effects of luteolin. Interestingly, these proteins included peroxiredoxin 6 (PRDX6) and prohibitin (PHB), which are implicated in ROS metabolism and apoptosis. Western blot analyses confirmed the expression of these proteins in Huh-7 cells following luteolin application. On the basis of these results, we suggest that PRDX6 and PHB are key targets of luteolin that the mechanism of luteolin-induced apoptosis in Huh-7 cells is mediated through effects involving intracellular ROS.
木犀草素已被证明对多种癌症具有抗癌活性，包括人类肝癌。许多体外研究报道了木犀草素的抗氧化作用。在此，我们通过在人肝癌细胞系Huh-7中检测活性氧（ROS），证明木犀草素的抗癌作用是通过增加细胞内ROS水平介导的。为了鉴定可能参与该机制的蛋白质，采用了基于二维电泳（2-DE）的蛋白质组学方法。蛋白质组学分析表明，几种蛋白质与木犀草素的抗癌作用有关。有趣的是，这些蛋白质包括过氧化物酶体增殖物激活受体6（PRDX6）和抑制素（PHB），它们与ROS代谢和细胞凋亡有关。蛋白质印迹分析证实了木犀草素作用后Huh-7细胞中这些蛋白质的表达。基于这些结果，我们认为PRDX6和PHB是木犀草素的关键靶点，木犀草素诱导Huh-7细胞凋亡的机制是通过涉及细胞内ROS的作用介导的。
