Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo
Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo
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DOI：
10.1016/j.canlet.2006.01.027
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发表时间：
2007-01-08
期刊：
影响因子：
9.7
通讯作者：
Maheshwari, Radha K.
中科院分区：
文献类型：
--
作者：
Thangapazham, Rajesh L.;Singh, Anoop K.;Maheshwari, Radha K.
作为一种饮料，茶（茶树科）的摄入量仅次于水。在各种临床前动物模型中，绿茶多酚已被证明对前列腺癌有保护作用，据报道，它对其他几种癌症也有效。据报道，亚裔美国人患乳腺癌的风险与绿茶的摄入量呈负相关。几项流行病学研究表明，经常饮用绿茶的亚洲人群中，乳腺癌的进展被推迟了。在这项研究中，我们报告了绿茶多酚（GTP）及其成分表没食子儿茶素没食子酸酯（EGCG）在乳腺癌体外细胞培养模型和体内胸腺裸鼠模型中肿瘤消退的有效性。采用四氮唑染料法（MTT）研究了GTP和EGCG对人乳腺癌MDA-MB-231细胞生长的抑制作用。通过流式细胞术评估，GTP和EGCG治疗均能将细胞周期阻滞在G1期。与未处理的对照组相比，GTP和EGCG处理的实验组Cyclin D、Cyclin E、cdk4、cdk1和PCNA的表达随着时间的推移而下调，细胞周期蛋白的western blot分析证实了G1阻断。裸鼠接种人乳腺癌MDA-MB-231细胞，经GTP和EGCG处理后，与饮水和类似处理的对照组相比，能有效延缓肿瘤发生，减轻肿瘤负担。免疫组化检测肿瘤组织切片，发现GTP和EGCG均可诱导细胞凋亡，抑制细胞增殖。我们的研究结果表明，GTP和EGCG在体外和体内均能抑制MDA-MB-231细胞的增殖并诱导细胞凋亡。总之，这些数据支持我们GTP和EGCG具有抗肿瘤特性的论点。2006爱思唯尔爱尔兰有限公司版权所有。
Tea [Camellia sinensis (Theaceae)] intake is second only to water in terms of worldwide popularity as a beverage. The Green tea polyphenols have been shown to have a protective effect in prostate cancer in various pre-clinical animal models and has been reported to be effective in several other cancer types as well. An inverse association between the risk of breast cancer and the intake of green tea has also been reported in Asian Americans. Several epidemiological studies have shown that breast cancer progression is delayed in the Asian population that consumes green tea on regular basis. In this study, we report the effectiveness of green tea polyphenols (GTP) and its constituent Epigallocatechin Gallate (EGCG) in tumor regression using both in-vitro cell culture models and in vivo athymic nude mice models of breast cancer. The anti-proliferative effect of GTP and EGCG on the growth of human breast cancer MDA-MB-231 cell was studied using a tetrazolium dye-based (MTT) assay. Both GTP and EGCG treatment had the ability to arrest the cell cycle at G1 phase as assessed by flow cytometry. The expression of Cyclin D, Cyclin E, CDK 4, CDK 1 and PCNA were down regulated over the time in GTP and EGCG treated experimental group, compared to the untreated control group as evaluated by western blot analysis for cell cycle proteins, which corroborated the G1 block. Nude mice inoculated with human breast cancer MDA-MB-231 cells and treated with GTP and EGCG were effective in delaying the tumor incidence as well as reducing the tumor burden when compared to the water fed and similarly handled control. GTP and EGCG treatment were also found to induce apoptosis and inhibit the proliferation when the tumor tissue sections were examined by immunohistochemistry. Our results suggest that GTP and EGCG treatment inhibits proliferation and induce apoptosis of MDA-MB-231 cells in-vitro and in-vivo. All together, these data sustain our contention that GTP and EGCG have anti-tumor properties. (c) 2006 Elsevier Ireland Ltd. All rights reserved.