Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells
Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells
复制标题
DOI：
10.1002/ijc.21932
复制
发表时间：
2006-08-15
影响因子：
6.4
通讯作者：
Huang, Shile
中科院分区：
文献类型：
--
作者：
Beevers, Christopher S.;Li, Fengjun;Huang, Shile
姜黄素（二阿魏酰甲烷），植物姜黄的多酚天然产物，正在进行早期的临床试验作为一种新的抗癌剂。然而，姜黄素的抗癌机制仍有待阐明。在这里，我们表明，姜黄素抑制横纹肌肉瘤细胞（Rh 1和Rh 30）的生长（IC 50 = 2-5 μ M），并在细胞周期的G（1）期逮捕细胞。姜黄素还诱导细胞凋亡，并抑制基础或I型胰岛素样生长因子诱导的细胞运动。在生理浓度（类似于2.5 μ M）。姜黄素快速抑制哺乳动物雷帕霉素靶（mTOR）和kit下游效应分子的磷酸化。p70 S6激酶1（S6 K1）和真核起始因子4 E（eIF 4 E）结合蛋白1（4 E-BP 1）。在一组细胞系（Rh 1，Rh 30，DU 145. MCF-7和Hela）。姜黄素还抑制细胞中Akt的磷酸化。但仅在高浓度（> 40 μ M）下。这些数据表明，姜黄素可能主要通过阻断肿瘤细胞中mTOR介导的信号通路来执行其抗癌活性。(c)2006 Wiley-Liss，Inc.
Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma longa, is undergoing early clinical trials as a novel anticancer agent. However, the anticancer mechanism of curcumin remains to be elucidated. Here we show that curcumin inhibited growth of rhabdomyosarcoma cells (Rh1 and Rh30) (IC50 = 2-5 mu M) and arrested cells in G(1) phase of the cell cycle. Curcumin also induced apoptosis and inhibited the basal or type I insulin-like growth factor-induced motility of the cells. At physiological concentrations (similar to 2.5 mu M). curcumin rapidly inhibited phosphorylation of the mammalian target of rapamycin (mTOR) and kits downstream effector molecules. p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1). in a panel of cell lines (Rh1, Rh30, DU145. MCF-7 and Hela). Curcumin also inhibited phosphorylation of Akt in the cells. but only at high concentrations (> 40 mu M). The data suggest that curcumin may execute its anticancer activity primarily by blocking mTOR-mediated signaling pathways in the tumor cells. (c) 2006 Wiley-Liss, Inc.