肝细胞生长因子
蛋白激酶B
没食子酸表没食子酸酯
MAPK/ERK通路
儿茶素
癌症研究
运动性
信号转导
生物
绿茶提取物
细胞培养
细胞生长
药理学
细胞生物学
生物化学
受体
绿茶
多酚
抗氧化剂
食品科学
遗传学
作者
Rebecca L. Bigelow,James A. Cardelli
出处
期刊:Oncogene
[Springer Nature]
日期:2006-03-01
卷期号:25 (13): 1922-1930
被引量:127
标识
DOI:10.1038/sj.onc.1209227
摘要
The hepatocyte growth factor (HGF) receptor, Met, is a strong prognostic indicator of breast cancer patient outcome and survival, suggesting that therapies targeting Met may have beneficial outcomes in the clinic. (−)-Epigallocatechin-3-gallate (EGCG), a catechin found in green tea, has been recognized as a potential therapeutic agent. We assessed the ability of EGCG to inhibit HGF signaling in the immortalized, nontumorigenic breast cell line, MCF10A, and the invasive breast carcinoma cell line, MDA-MB-231. HGF treatment in both cell lines induced rapid, sustained activation of Met, ERK and AKT. Pretreatment of cells with concentrations of EGCG as low as 0.3 μ M inhibited HGF-induced Met phosphorylation and downstream activation of AKT and ERK. Treatment with 5.0 μ M EGCG blocked the ability of HGF to induce cell motility and invasion. We assessed the ability of alternative green tea catechins to inhibit HGF-induced signaling and motility. (−)-Epicatechin-3-gallate (ECG) functioned similar to EGCG by completely blocking HGF-induced signaling as low as 0.6 μ M and motility at 5 μ M in MCF10A cells; whereas, (−)-epicatechin (EC) was unable to inhibit HGF-induced events at any concentration tested. (−)-Epigallocatechin (EGC), however, completely repressed HGF-induced AKT and ERK phosphorylation at concentrations of 10 and 20 μ M, but was incapable of blocking Met activation. Despite these observations, EGC did inhibit HGF-induced motility in MCF10A cells at 10 μ M. These observations suggest that the R1 galloyl and the R2 hydroxyl groups are important in mediating the green tea catechins' inhibitory effect towards HGF/Met signaling. These combined in vitro studies reveal the possible benefits of green tea polyphenols as cancer therapeutic agents to inhibit Met signaling and potentially block invasive cancer growth.
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