Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway
Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway
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DOI：
10.1016/j.canlet.2006.03.030
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发表时间：
2007-03-08
期刊：
影响因子：
9.7
通讯作者：
Park, Ock Jin
中科院分区：
文献类型：
--
作者：
Hwang, Jin-Taek;Ha, Joohun;Park, Ock Jin
EGCG[（-）表没食子儿茶素-3-没食子酸酯]是一种绿茶衍生的多酚，已被证明可以抑制癌细胞增殖，干扰多种信号通路并诱导细胞凋亡。实际上，越来越多的证据表明，EGCG有可能提高患者化疗的疗效。我们假设EGCG可能通过调节AMPK （amp活化蛋白激酶），随后降低COX-2的表达来发挥细胞毒性。EGCG对结肠癌细胞的处理导致AMPK的强烈激活和COX-2的表达抑制。通过使用AMPK抑制剂化合物c抑制AMPK，可以完全消除EGCG降低的COX-2表达和前列腺素E-2分泌。此外，在EGCG处理的癌细胞中，AMPK的激活伴随着血管内皮生长因子（VEGF）和葡萄糖转运蛋白Glut-1的降低。这些发现支持AMPK在egcg处理的癌细胞中对COX-2表达的调节作用。此外，我们还发现活性氧（ROS）是AMPK的上游信号，EGCG与化疗药物5-FU或依托泊苷联合治疗对化疗耐药结肠癌细胞有新的治疗效果。AMPK是一种新定义的癌症靶标分子，被证明可以控制egcg处理的结肠癌细胞中的COX-2。2006爱思唯尔爱尔兰有限公司版权所有。
EGCG [(-)epigallocatechin-3-gallate], a green tea-derived polyphenol, has been shown to suppress cancer cell proliferation, and interfere with the several signaling pathways and induce apoptosis. Practically, there is emerging evidence that EGCG has a potential to increase the efficacy of chemotherapy in patients. We hypothesized that EGCG may exert cell cytotoxicity through modulating AMPK (AMP-activated protein kinase) followed by the decrease in COX-2 expression. EGCG treatment to colon cancer cells resulted in a strong activation of AMPK and an inhibition of COX-2 expression. The decreased COX-2 expression as well as prostaglandin E-2 secretion by EGCG was completely abolished by inhibiting AMPK by an AMPK inhibitor, Compound C. Also, the activation of AMPK was accompanied with the reduction of VEGF (vascular endothelial growth factor) and glucose transporter, Glut-1 in EGCG-treated cancer cells. These findings support the regulatory role of AMPK in COX-2 expression in EGCG-treated cancer cells. Furthermore, we have found that reactive oxygen species (ROS) is an upstream signal of AMPK, and the combined treatment of EGCG and chemotherapeutic agents, 5-FU or Etoposide, exert a novel therapeutic effect on chemoresistant colon cancer cells. AMPK, a molecule of newly defined cancer target, was shown to control COX-2 in EGCG-treated colon cancer cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.