Butein induces G2/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation
Butein induces G2/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation
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DOI：
10.1016/j.canlet.2009.07.002
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发表时间：
2010-02-28
期刊：
影响因子：
9.7
通讯作者：
Kim, Gi-Young
中科院分区：
文献类型：
--
作者：
Moon, Dong-Oh;Kim, Mun-Ock;Kim, Gi-Young
我们研究了3,4,2',4'-四羟基查尔酮（丁蛋白）对两种人肝癌细胞系hepg2和Hep3B的分子效应。Butein通过诱导G(2)/M期阻滞和细胞凋亡抑制癌细胞生长。butein诱导的G(2)/M相阻滞与ATM、Chk1和Chk2磷酸化增加以及cdc25C水平降低有关。此外，蛋白处理增强了失活的磷酸化-Cdc2水平，降低了Cdc2激酶活性，并产生活性氧（ROS），伴随着JNK的激活。用n-乙酰- l-半胱氨酸或谷胱甘肽预处理和SP600125降低JNK磷酸化后，丁蛋白诱导的G(2)/M相阻滞程度显著降低。n-乙酰- l-半胱氨酸和谷胱甘肽均可减少丁蛋白介导的细胞凋亡。综上所述，这些结果暗示了ROS和JNK在蛋白抗癌作用中的关键作用。2009爱思唯尔爱尔兰有限公司版权所有。
We investigated the molecular effects of 3,4,2',4'-tetrahydroxychalcone (butein) treatment in two human hepatoma cancer cell lines-HepG2 and Hep3B. Butein treatment inhibited cancer cell growth by inducing G(2)/M phase arrest and apoptosis. Butein-induced G(2)/M phase arrest was associated with increased ATM, Chk1, and Chk2 phosphorylations and reduced cdc25C levels. Additionally, butein treatment enhanced inactivated phospho-Cdc2 levels, reduced Cdc2 kinase activity, and generated reactive oxygen species (ROS) that was accompanied by JNK activation. The extent of butein-induced G(2)/M phase arrest significantly decreased following pretreatment with N-acetyl-L-cysteine or glutathione and following JNK phosphorylation reduction by SP600125. Both N-acetyl-L-cysteine and glutathione also decreased butein-mediated apoptosis. Taken together, these results imply a critical role of ROS and JNK in the anticancer effects of butein. (C) 2009 Elsevier Ireland Ltd. All rights reserved.