Anti-proliferative effects of green tea polyphenol EGCG on Ha-Ras-induced transformation of intestinal epithelial cells

Oncogenic Ras mutations are frequently observed in colorectal cancer and participate in neoplastic transformation of intestinal epithelial cells. Accumulating evidence demonstrates the chemopreventive properties of green tea on colon carcinogenesis. Here we investigated the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), to inhibit proliferation of intestinal epithelial cells (RIE-1) transfected with an inducible Ha-RasVal12 cDNA. EGCG inhibited cell proliferation induced by oncogenic Ras and blocked cell cycle transition at G1 phase via inhibition of cyclin D1 expression. The EGCG IC50 was 42 μM in transformed cells and 81 μM in non-transformed cells. EGCG also promoted E-cadherin expression, which is downregulated by Ras transformation. This study demonstrates the potential of the natural compound EGCG as an effective adjuvant therapy for colon tumors bearing Ras mutations.