藤黄酸
化学
热休克蛋白90
细胞凋亡
细胞生物学
NF-κB
癌症研究
赫拉
蛋白激酶B
磷酸化
生物
肿瘤坏死因子α
细胞培养
信号转导
分子生物学
细胞生长
癌细胞
下调和上调
活力测定
细胞毒性
αBκ
作者
Lianru Zhang,Yuting Yi,Junjie Chen,Yifei Sun,Qiuju Guo,Zhuo Zheng,Shuai Song
标识
DOI:10.1016/j.bbrc.2010.11.018
摘要
Gambogic acid (GB) is an important anti-cancer drug candidate, but the target protein by which it exerts its anti-cancer effects has not been identified. This study is the first to show that GB inhibits heat shock protein 90 (Hsp90) and down-regulates TNF-α/NF-κB in HeLa cells. The effects of GB on Hsp90 were studied by characterizing its physical interactions with Hsp90 upon binding, the noncompetitive inhibition of Hsp90 ATPase activity, and the degradation of Hsp90 client proteins (i.e., Akt, IKK) in HeLa cells. GB seems to bind to the N-terminal ATP-binding domain of Hsp90. Additionally, GB suppresses the activation of TNF-α/NF-κB and decreases XIAP expression levels and the ratio of Bcl-2/Bax, which in turn induces HeLa cell apoptosis. Thus, GB represents a promising therapeutic agent for cancer; it may also be useful as a probe to increase understanding of the biological functions of Hsp90.
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