Inhibition of β-catenin signaling in human colon cancer cells and ApcMin mice by (-)-Epigallocatechin-3-gallate

Proc Amer Assoc Cancer Res, Volume 47, 2006 4889 Previously, we reported that oral administration of (-)-epigallocatechin-3-gallate (EGCG), a major catechin in green tea, not only inhibited small intestinal tumor formation in Apc Min mice but also resulted in decreases of nuclear β-catenin and c-Myc levels and increases of E-cadherin levels in small intestinal tumors (Cancer Res, 2005; 65(22): in press) . The purpose of present study was to investigate mechanisms involved in the inhibition of aberrant β-catenin signaling by EGCG in vitro and in vivo . In HCT116 human colon cancer cells, treatment with EGCG at concentrations of 20, 50, and 100 μM decreased the levels of nuclear β-catenin but increased the levels of E-cadherin, which is a similar finding to our previous results in another human colon cancer cell line, HT29 (Cancer Res, 2005; 65(22): in press) . The EGCG treatment also suppressed important upstream events for the release of β-catenin from plasma membrane to cytoplasm and the degradation of E-cadherin; levels of tyrosine phosphorylation of β-catenin and p120ctn as well as the phosphorylation (Thr 12) of Fyn were decreased under the EGCG treatment. In studies with 14-week old Apc Min/+ mice, small intestinal tumors were found to have higher levels of IGF-1R and Fyn than normal small intestine tissues. In both normal and tumor tissues from Apc Min/+ mice that were given intragastric administration of EGCG (75 mg/kg) 3 h before sacrifice, phosphorylation levels of IGF-1R, Fyn, β-catenin, and p120ctn were decreased as compared to the levels in the normal and tumor tissues from control mice. These results suggest that EGCG suppresses abberant β-catenin signaling possibly through inhibition of phosphorylation of β-catenin, p120ctn, IGF-1R, and Fyn, and these effects may contribute to the inhibition of tumorigenesis in Apc Min mice (supported by NIH grant CA 88961) .