EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism
EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism
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DOI：
10.1097/00001813-200503000-00005
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发表时间：
2005-03-01
影响因子：
2.3
通讯作者：
Shoji, M
中科院分区：
文献类型：
--
作者：
Adams, BK;Cai, JY;Shoji, M
在这项研究中，我们表明，新的合成姜黄素类似物，EF 24，诱导细胞周期停滞和凋亡的氧化还原依赖性机制的装置在MDA-MB-231人乳腺癌细胞和DU-145人前列腺癌细胞。细胞周期分析表明，EF 24导致两种细胞系中的G（2）/M停滞，并且该细胞周期停滞之后是凋亡的诱导，如通过半胱天冬酶-3活化、磷脂酰丝氨酸外化和具有亚G，DNA部分的细胞数量增加所证明的。此外，我们证明，EF 24诱导线粒体膜电位的去极化，这表明该化合物也可能通过改变线粒体功能诱导细胞凋亡。EF 24与姜黄素一样，作为与谷胱甘肽（GSH）和硫氧还蛋白1反应的迈克尔受体。EF 24与这些试剂的体内反应显著降低了野生型和过表达Bcl-x（L）的HT 29人结肠癌细胞中的细胞内GSH以及氧化GSH。因此，我们提出，一种新的姜黄素类似物，EF 24的抗癌作用，介导的部分氧化还原介导的诱导细胞凋亡。(C)2005年利平科特威廉姆斯威尔金斯。
In this study, we show that the novel synthetic curcumin analog, EF24, induces cell cycle arrest and apoptosis by means of a redox-dependent mechanism in MDA-MB-231 human breast cancer cells and DU-145 human prostate cancer cells. Cell cycle analysis demonstrated that EF24 causes a G(2)/M arrest in both cell lines, and that this cell cycle arrest is followed by the induction of apoptosis as evidenced by caspase-3 activation, phosphatidylserine externalization and an increased number of cells with a sub-G, DNA fraction. In addition, we demonstrate that EF24 induces a depolarization of the mitochondrial membrane potential, suggesting that the compound may also induce apoptosis by altering mitochondrial function. EF24, like curcumin, serves as a Michael acceptor reacting with glutathione (GSH) and thioredoxin 1. Reaction of EF24 with these agents in vivo significantly reduced intracellular GSH as well as oxidized GSH in both the wild-type and Bcl-x(L) overexpressing HT29 human colon cancer cells. We therefore propose that the anticancer effect of a novel curcumin analog, EF24, is mediated in part by redox-mediated induction of apoptosis. (C) 2005 Lippincott Williams Wilkins.