Abrogation of Akt signaling by Isobavachalcone contributes to its anti-proliferative effects towards human cancer cells

被引：91

作者：

Jing, Hui ^{[1
]}

Zhou, Xinglu ^{[1
]}

Dong, Xiaowu ^{[2
]}

Cao, Ji ^{[1
]}

Zhu, Hong ^{[1
]}

Lou, Jianshu ^{[1
]}

Hu, Yongzhou ^{[2
]}

He, Qiaojun ^{[1
]}

Yang, Bo ^{[1
]}

机构：

[1] Zhejiang Univ, Sch Pharmaceut Sci, Inst Pharmacol & Toxicol, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sch Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou 310058, Zhejiang, Peoples R China

来源：

CANCER LETTERS | 2010年 / 294卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Isobavachalcone; Akt; Computational simulation; Anti-proliferative effect; Chemotherapy; PROTEIN-KINASE-B; PI3K/AKT PATHWAY; DRUG DISCOVERY; ANTITUMOR-ACTIVITY; MOLECULAR-CLONING; ANGELICA-KEISKEI; NATURAL-PRODUCTS; PHOSPHORYLATION; INHIBITOR; INSULIN;

D O I：

10.1016/j.canlet.2010.01.035

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：167 / 177

页数：11

共 56 条

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