Cell cycle arrest and apoptosis induced by methyl 3,5-dicaffeoyl quinate in human colon cancer cells: Involvement of the PI3K/Akt and MAP kinase pathways
Cell cycle arrest and apoptosis induced by methyl 3,5-dicaffeoyl quinate in human colon cancer cells: Involvement of the PI3K/Akt and MAP kinase pathways
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DOI：
10.1016/j.cbi.2011.08.006
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发表时间：
2011-10-15
影响因子：
5.1
通讯作者：
Wang, Myeong-Hyeon
中科院分区：
文献类型：
--
作者：
Hu, Weicheng;Shen, Ting;Wang, Myeong-Hyeon
3，5-二咖啡酰奎尼酸甲酯（MDQ）是一种黄酮苷类化合物，存在于多种植物中，能清除DPPH自由基和过氧亚硝酸根，抑制铜离子诱导的大鼠血浆氧化过程中胆固醇酯过氧化氢的形成。在这项研究中，MDQ抑制增殖和诱导HT-29细胞凋亡的剂量依赖性的方式检测1-（4，5-二甲基噻唑-2-基）-3，5-二苯基甲（MTT），台盼蓝拒染法，流式细胞仪检测。Western blot分析显示凋亡依赖于caspase-3活性。PARP裂解和细胞色素c从线粒体的胞质释放显着增加。此外，这些事件伴随着线粒体膜电位的崩溃和Bcl-2/Bax比值的降低。此外，MDQ诱导的G（0）/G（1）阻滞与p27的增加和cyclin D1和p53的减少相关。MDQ还抑制PI 3 K/Akt和ERK的磷酸化：显著降低NF-κ B B;并且通常通过HT-29细胞中的细胞周期停滞和凋亡诱导显示显著的抗增殖作用。这些结果表明MDQ对人结肠癌具有治疗潜力。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Methyl 3,5-dicaffeoyl quinate (MDQ) is a flavonoid glucoside found in several plants that scavenges 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and peroxynitrite, and inhibits the formation of cholesteryl ester hydroperoxide during the copper ion-induced oxidation of blood plasma in rats. In this study, MDQ inhibited proliferation and induced apoptosis in HT-29 cells in a dose-dependent manner as detected by 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT), trypan blue exclusion, and flow cytometric assays. Western blot analysis showed that apoptosis was dependent on caspase-3 activity. PARP cleavage and the cytosolic release of cytochrome c from mitochondria increased significantly. In addition, these events were accompanied by a collapse in the mitochondrial membrane potential and a decreased Bcl-2/Bax ratio. Furthermore, the MDQ-induced G(0)/G(1) arrest was correlated with an increase in p27 and a decrease in cyclin D1 and p53. MDQ also inhibited the phosphorylation of PI3K/Akt and ERK: significantly reduced NF-kappa B; and in general displayed a significant anti-proliferative effect via a cell cycle arrest and apoptotic induction in HT-29 cells. These results suggest that MDQ has therapeutic potential against human colon carcinoma. (C) 2011 Elsevier Ireland Ltd. All rights reserved.