Inhibition of catechol-Omicron-methyltransferase activity in human breast cancer cells enhances the biological effect of the green tea polyphenol (-)-EGCG.
Inhibition of catechol-Omicron-methyltransferase activity in human breast cancer cells enhances the biological effect of the green tea polyphenol (-)-EGCG.
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DOI：
10.3892/or_00000893
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发表时间：
2010-08
期刊：
影响因子：
4.2
通讯作者：
Dou QP
中科院分区：
文献类型：
--
作者：
Landis-Piwowar K;Chen D;Chan TH;Dou QP
茶是世界上最受欢迎的饮料之一，作为一种促进健康的饮料被广泛研究，可能会预防一些慢性病和癌症。(-)-表没食子儿茶素没食子酸酯[(-)-EGCG]是绿茶中的主要成分，在生理条件下不稳定，儿茶酚-O-甲基转移酶(COMT)对(-)-EGCG的甲基化是一种降低(-)-EGCG生物活性的修饰。在目前的研究中，我们假设抑制人乳腺癌细胞中COMT的活性可以增加(-)-EGCG的蛋白酶体抑制能力，从而增强其对肿瘤细胞的生长抑制活性。我们首先确定了不同的人类乳腺癌细胞系的COMT基因和COMT活性的基础水平。此外，当检测含有高COMT活性的乳腺癌MDA-MB-231细胞时，COMT活性的降低明显增强了(-)-EGCG的有效性，这是通过增强蛋白酶体抑制和诱导细胞凋亡来实现的。这项研究补充了以前的发现，即甲基化(-)-EGCG生物活性较低，并支持COMT抑制可能增加茶多酚的抗癌特性的观点，该组合可能作为乳腺癌化疗的一种新方法或补充治疗。
Tea is one of the most popular beverages in the world and has been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. (-)-Epigallocatechin gallate [(-)-EGCG], a major component in green tea, is unstable under physiological conditions and methylation of (-)-EGCG by catechol-O-methyltransferase (COMT) is a modification that reduces the biological activity of (-)-EGCG. In the current study, we hypothesized that suppression of COMT activity in human breast cancer cells could increase the proteasome-inhibitory potency of (-)-EGCG and therefore enhance its tumor cell growth-inhibitory activity. We first determined the COMT genotype and basal levels of COMT activity in various human breast cancer cell lines. Furthermore, when breast cancer MDA-MB-231 cells containing high COMT activity were tested, the diminished COMT activity apparently increased the effectiveness of (-)-EGCG via augmented proteasome inhibition and apoptosis induction. This study supplements the previous findings that methylated (-)-EGCG is less bioactive and supports the notion that COMT inhibition may increase the anti-cancer properties of tea polyphenols and the combination may serve as a novel approach or supplemental treatment for breast cancer chemotherapy.
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DOI：
10.1007/s00432-007-0244-7
发表时间：
2007-12-01
影响因子：
3.6
作者：
Hu, Zhen;Song, Chuan-Gui;Shao, Zhi-Ming
通讯作者：
Shao, Zhi-Ming
影响因子：
9.7
作者：
LIAO, SS;UMEKITA, Y;HIIPAKKA, RA
通讯作者：
HIIPAKKA, RA
影响因子：
5.6
作者：
Landis-Piwowar, Kristin R.;Wan, Sheng Biao;Dou, Q. Ping
通讯作者：
Dou, Q. Ping
DOI：
10.1073/pnas.94.20.10937
发表时间：
1997-09-30
影响因子：
11.1
作者：
Cavalieri, EL;Stack, DE;Rogan, EG
通讯作者：
Rogan, EG
影响因子：
12.4
作者：
An, B;Goldfarb, RH;Dou, QP
通讯作者：
Dou, QP