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Green tea polyphenol (-)-epigallocatechin-3-gallate inhibits cyclooxygenase-2 expression in colon carcinogenesis
Guang Peng1, Dan A Dixon, Stephanie J Muga
1Department of Pathology and Microbiology, School of Medicine, The University of South Carolina, and South Carolina Cancer Center, Columbia, South Carolina 29203, USA.
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 down regulated 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 kappaB (NF-kappaB) 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.
Insights
Green tea
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Green tea consumption is linked to anti-cancer effects, particularly in colon cancer.
- Cyclooxygenase-2 (COX-2) overexpression is implicated in colon cancer development.
- Non-steroidal anti-inflammatory drugs (NSAIDs) show chemopreventive potential by inhibiting COX-2.
Purpose of the Study:
- To investigate if green tea's anti-cancer properties involve the modulation of COX-2 expression.
- To determine the specific mechanisms by which green tea polyphenols affect COX-2 in colon cancer cells.
Main Methods:
- Human colorectal cancer cell lines (HT-29 and HCA-7) were treated with (-)-epigallocatechin-3-gallate (EGCG).
- Analysis of COX-2 mRNA and protein levels, signaling pathways (ERK1/2, Akt), and NF-kappaB activation.
- Investigation of COX-2 promoter activity and mRNA decay via the 3'UTR.
Main Results:
- EGCG significantly inhibited both COX-2 mRNA and protein overexpression in colon cancer cells.
- EGCG downregulated the ERK1/2 and Akt signaling pathways.
- EGCG reduced COX-2 promoter activity by inhibiting NF-kappaB activation and promoted mRNA decay.
Conclusions:
- Inhibition of COX-2 is a key mechanism underlying green tea's anti-proliferative effects in colon cancer.
- Dietary factors like green tea polyphenols play a significant role as anti-cancer agents.
- EGCG's multifaceted action on COX-2 regulation highlights its therapeutic potential.
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