Suppression of Met activation in human colon cancer cells treated with (−)-epigallocatechin-3-gallate: Minor role of hydrogen peroxide

Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. Met, the receptor for hepatocyte growth factor (HGF), is over-expressed in colon tumors and is associated with poor prognosis. Recently, the green tea polyphenol (−)-epigallocatechin gallate (EGCG) was reported to suppress Met activation in breast cancer cells. However, the possible confounding effect of hydrogen peroxide (H₂O₂), produced when EGCG is added to cell culture media, was not assessed. In the present study, the human colon cancer cell lines HCT116 and HT29 were used to examine the relationships between Met activation, EGCG treatment, and H₂O₂ generation. At concentrations of 0.5, 1, and 5 μM, EGCG suppressed markedly the activation of Met in the presence of HGF. Concentrations of 10 μM EGCG and below generated low amounts of H₂O₂ (<1.5 μM), whereas higher H₂O₂ concentrations (>5 μM) were required to directly increase the phosphorylation of Met. Moreover, suppression of Met activation by EGCG occurred in the presence or absence of catalase, suggesting that such effects were not an ‘artifact’ of H₂O₂ generated from EGCG in cell culture media. We conclude that EGCG might be a beneficial therapeutic agent in the colon, inhibiting Met signaling and helping to attenuate tumor spread/metastasis, independent of H₂O₂-related mechanisms.