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Inhibition of phorbol ester-induced COX-2 expression by epigallocatechin gallate in mouse skin and cultured human mammary epithelial cells

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Authors
Kundu, Joydeb Kumar; Na, Hye-Kyung; Chun, Kyung-Soo; Kim, Young-Kyung; Lee, Sang Jun; Lee, Sang Sup; Lee, Ok-Sub; Sim, Young-Chul; Surh, Young-Joon
Issue Date
2003-11
Citation
Journal of Nutrition, Vol.133 No.11, pp.3805S-3810S
Keywords
chemopreventionepigallocatechin gallate (EGCG)cyclooxygenase-2 (COX-2)mitogenactivated protein kinase (MAPK)human mammary epithelial cell (MCF-10A) mouse skin carcinogenesis
Abstract
Green tea polyphenols are reported to possess substantial antiinflammatory and chemopreventive properties. However, the molecular mechanism of chemopreventive activity of green tea polyphenols is not fully understood. An abnormally elevated level of cyclooxygenase-2 (COX-2) is implicated in the pathogenesis of carcinogenesis. In the present study, we found that pretreatment of the green tea extract enriched with catechin and epigallocatechin gallate (EGCG) by gavage inhibited COX-2 expression induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse skin. Similarly, EGCG downregulated COX-2 in TPA-stimulated human mammary epithelial cells (MCF-10A) in culture. To further elucidate the underlying mechanism of COX-2 inhibition by green tea extract and EGCG, we examined their effects on the activation of extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), which are upstream enzymes known to regulate COX-2 expression in many cell types. Pretreatment with EGCG as well as green tea extract caused a decrease in the activation of ERK. In addition, EGCG inhibited the catalytic activity of ERK and p38 MAPK, suggesting that these signal-transducing enzymes could be potential targets for previously reported antitumor promoting activity of EGCG.
ISSN
0022-3166
URI
https://hdl.handle.net/10371/172800
DOI
https://doi.org/10.1093/jn/133.11.3805S
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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