Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells
Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells
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DOI：
10.1016/j.canlet.2012.01.008
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发表时间：
2012-06-28
期刊：
影响因子：
9.7
通讯作者：
Kim, Sung-Hoon
中科院分区：
文献类型：
--
作者：
Jang, Ki Young;Jeong, Soo-Jin;Kim, Sung-Hoon
我们研究了Fesetin诱导U266细胞凋亡的分子机制。非瑟素对U266细胞有明显的细胞毒作用，表现为亚G1期细胞比例增加或TUNEL染色阳性。菲斯汀增强caspase-3活性，下调Bcl2和Mcl-1(L)，上调Bax、Rim和Bad。非瑟素可激活AMPK及其底物乙酰辅酶A羧化酶(ACC)，同时降低ALA和mTOR的磷酸化水平。非瑟素还能刺激U266细胞产生ROS。反之，化合物C或N-乙酰-L-半胱氨酸可阻断鱼腥草素诱导的细胞凋亡。我们的数据表明，Fesetin通过ROS和AMPK途径诱导U266细胞的凋亡。(C)2012爱思唯尔爱尔兰有限公司。保留所有权利。
We investigated the molecular mechanisms responsible for fisetin-induced apoptosis in U266 cells. Fisetin elicited the cytotoxicity in U266 cells, manifested as an increased fraction of the cells with sub-G1 content or stained positively with TUNEL labeling. Fisetin enhanced caspase-3 activation, downregulation of Bcl-2 and Mcl-1(L), and upregulation of Bax, Rim and Bad. Fisetin activated AMPK as well as its substrate acetyl-CoA carboxylase (ACC), along with a decreased phosphorylation of Ala and mTOR. Fisetin also stimulated generation of ROS in U266 cells. Conversely, compound C or N-acetyl-L-cystein blocked fisetin-induced apoptosis. Our data suggest that fisetin-induced apoptosis in U266 cells is through ROS and AMPK pathways. (C) 2012 Elsevier Ireland Ltd. All rights reserved.