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查耳酮可阻止细胞周期进程,并通过诱导线粒体途径和抑制人膀胱癌细胞中的核因子κB信号传导来诱导细胞凋亡。

Chalcone arrests cell cycle progression and induces apoptosis through induction of mitochondrial pathway and inhibition of nuclear factor kappa B signalling in human bladder cancer cells.

作者信息

Shen Kun-Hung, Chang Jiunn-Kae, Hsu Ya-Ling, Kuo Po-Lin

机构信息

Cell Biology Laboratory, Department of Biotechnology, Chia Nan University of Pharmacy and Science, 60 Erh-Jen Road Sec. 1, Jen-Te, Tainan 717, Taiwan.

出版信息

Basic Clin Pharmacol Toxicol. 2007 Oct;101(4):254-61. doi: 10.1111/j.1742-7843.2007.00120.x.

Abstract

Chalcones (1,3-diphenyl-2-propenone) are cancer preventive food components found in a human diet rich in fruits and vegetables. In this study, we first report the chemopreventive effect of chalcone in two human bladder cancer cell lines: T24 and HT-1376. The results show that chalcone inhibits the proliferation of T24 and HT-1376 cells by inducing apoptosis and blocking cell cycle progression in the G2/M phase. Western blot assay showed that chalcone significantly increases the expression of p21 and p27 proteins, and decreases the levels of cyclin B1, cyclin A and Cdc2, thereby contributing to cell cycle arrest. In addition, chalcone increased the expression of Bax and Bak, but decreased the levels of Bcl-2 and Bcl-X(L) and subsequently triggered mitochondrial apoptotic pathway (release of cytochrome c and activation of caspase-9 and caspase-3). Our study suggests that the induction of mitochondrial pathway and inhibition of the nuclear factor kappa B survival system may play important roles in the antiproliferative activity of chalcone in T24 and HT-1376 cells.

摘要

查耳酮(1,3 - 二苯基 - 2 - 丙烯酮)是在富含水果和蔬菜的人类饮食中发现的具有癌症预防作用的食物成分。在本研究中,我们首次报道了查耳酮对两种人膀胱癌细胞系T24和HT - 1376的化学预防作用。结果表明,查耳酮通过诱导细胞凋亡和阻断细胞周期在G2/M期的进程来抑制T24和HT - 1376细胞的增殖。蛋白质印迹分析表明,查耳酮显著增加p21和p27蛋白的表达,并降低细胞周期蛋白B1、细胞周期蛋白A和细胞周期蛋白依赖性激酶2(Cdc2)的水平,从而导致细胞周期停滞。此外,查耳酮增加了Bax和Bak的表达,但降低了Bcl - 2和Bcl - X(L)的水平,随后触发线粒体凋亡途径(细胞色素c的释放以及半胱天冬酶 - 9和半胱天冬酶 - 3的激活)。我们的研究表明,线粒体途径的诱导和核因子κB生存系统的抑制可能在查耳酮对T24和HT - 1376细胞的抗增殖活性中发挥重要作用。

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