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 (H(2)O(2)), 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 H(2)O(2) generation. At concentrations of 0.5, 1, and 5 microM, EGCG suppressed markedly the activation of Met in the presence of HGF. Concentrations of 10muM EGCG and below generated low amounts of H(2)O(2) (<1.5 microM), whereas higher H(2)O(2) concentrations (>5 microM) 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 H(2)O(2) 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 H(2)O(2)-related mechanisms.
Larsen
Christine A
CA
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA.
Dashwood
Roderick H
RH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D000975:Antioxidants; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met