Abrogation of Akt signaling by Isobavachalcone contributes to its anti-proliferative effects towards human cancer cells
Abrogation of Akt signaling by Isobavachalcone contributes to its anti-proliferative effects towards human cancer cells
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DOI：
10.1016/j.canlet.2010.01.035
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发表时间：
2010-08-28
期刊：
影响因子：
9.7
通讯作者：
Yang, Bo
中科院分区：
文献类型：
--
作者：
Jing, Hui;Zhou, Xinglu;Yang, Bo
Akt信号通路作为一种有前景的肿瘤治疗靶点而备受关注。本研究发现，天然查尔酮异巴伐恰尔酮（Isobavachalcone， IBC）可抑制Akt信号通路，并对多种人类癌细胞发挥抗增殖作用。Sybyl/FlexiDock程序的建模结果表明，IBC可能与Akt的atp结合口袋结合，IBC在体外抑制Akt1激酶的观察证实了这一点。进一步的研究表明，IBC显著降低了细胞中Ser-473位点的Akt磷酸化和Akt激酶活性，从而导致Akt下游底物的抑制，并引起与线粒体途径相关的显著水平的凋亡。2010爱思唯尔爱尔兰有限公司版权所有。
Akt signaling pathway has attracted much attention as a promising target for cancer therapeutics. Herein, we report that Isobavachalcone (IBC), a natural chalcone, potently abrogates Akt signaling and exerts anti-proliferative effects on several human cancer cell lines. Modeling results from the Sybyl/FlexiDock program suggest that IBC potentially binds to the ATP-binding pocket of Akt, which is confirmed by the observations that IBC inhibits Akt1 kinase in vitro. Further studies reveal that IBC significantly abates Akt phosphorylation at Ser-473 and Akt kinase activity in cells, which subsequently leads to inhibition of Akt downstream substrates and evokes significant levels of apoptosis associated with mitochondria pathway. (C) 2010 Elsevier Ireland Ltd. All rights reserved.