¹Department of Microbiology and Immunology, Feist-Weiller Cancer Center, Louisiana State University-Health Sciences Center, Shreveport, LA, USA

Correspondence: Dr JA Cardelli, Department of Microbiology and Immunology, Louisiana State University-Health Sciences Center-Shreveport, 1501 Kings Highway, Shreveport, LA 71130, USA. E-mail: jcarde@lsuhsc.edu

Received 24 June 2005; Revised 1 September 2005; Accepted 4 October 2005; Published online 30 January 2006.

Abstract

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 M inhibited HGF-induced Met phosphorylation and downstream activation of AKT and ERK. Treatment with 5.0 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 M and motility at 5 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 M, but was incapable of blocking Met activation. Despite these observations, EGC did inhibit HGF-induced motility in MCF10A cells at 10 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.