Inhibition of phorbol ester-induced COX-2 expression by epigallocatechin gallate in mouse skin and cultured human mammary epithelial cells.
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.
Kundu
Joydeb Kumar
JK
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Na
Hye-Kyung
HK
Chun
Kyung-Soo
KS
Kim
Young-Kyung
YK
Lee
Sang Jun
SJ
Lee
Sang Sup
SS
Lee
Ok-Sub
OS
Sim
Young-Chul
YC
Surh
Young-Joon
YJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001940:Breast / Q000166:cytology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics*; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D013662:Tea; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000633:toxicity*
D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013662:Tea; D002392:Catechin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C057580:gallocatechol; D013755:Tetradecanoylphorbol Acetate