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The green tea catechins, (−)-Epigallocatechin-3-gallate (EGCG) and (−)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells


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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(−)-epicatechin gallate






hepatocyte growth factor


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This work was supported through Grant NIH R01 CA104242-01.

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Correspondence to J A Cardelli.

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Bigelow, R., Cardelli, J. The green tea catechins, (−)-Epigallocatechin-3-gallate (EGCG) and (−)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene 25, 1922–1930 (2006).

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