Abstract
Tea, one of the most widely consumed beverages worldwide, has been shown to have anti‐cancer activity in various cancers including colon cancer. It has been demonstrated that overexpression of the inducible isoform of cyclooxygenase (COX‐2) occurs during colon tumorigenesis and inhibition of COX‐2 by non‐steroidal anti‐inflammatory drugs (NSAIDs) is chemopreventive. To determine whether the anti‐cancer effect associated with green tea impacted COX‐2 expression levels, human colorectal cancer cell lines HT‐29 and HCA‐7, were treated with (−)‐epigallocatechin‐3‐gallate (EGCG), the most abundant and effective polyphenol of green tea. EGCG significantly inhibited constitutive COX‐2 mRNA and protein overexpression. The inhibitory effects of EGCG on signaling pathways controlling COX‐2 expression were examined. We observed that EGCG downregulated the ERK1/2 and Akt pathways in colon cancer cells. The effect of EGCG on COX‐2 expression resulted in decreased COX‐2 promoter activity via inhibition of nuclear factor κB (NF‐κB) activation. EGCG also promoted rapid mRNA decay mediated through the COX‐2 3′untranslated region (3′UTR). In conclusion, these data suggest that inhibition of COX‐2 is a mechanism for the anti‐proliferative effect of green tea and emphasizes the role that dietary factors have as anti‐cancer agents. © 2006 Wiley‐Liss, Inc.