期刊
MOLECULAR CARCINOGENESIS
卷 45, 期 5, 页码 309-319出版社
WILEY-LISS
DOI: 10.1002/mc.20166
关键词
EGCG; COX-2; gene expression; NF-kappa B; MAPKs; colon cancer cells
资金
- NCI NIH HHS [R01CA096694] Funding Source: Medline
- NCRR NIH HHS [P20RR17698] Funding Source: Medline
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 kappa B (NF-kappa B) 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. (c) 2006 Wiley-Liss, Inc.
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