Inhibition of Phorbol Ester–Induced COX-2 Expression by Epigallocatechin Gallate in Mouse Skin and Cultured Human Mammary Epithelial Cells

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.

Epicatechin enhances anti-proliferative effect of bleomycin in ovarian cancer cell

“…Untreated and treated SKOV-3 and HFFF2 cells were subjected to cell proliferation assay using MTT to quantify the metabolic activity to cleave tetrazolium salts (18,19). Cells (20,000) were seeded in 96-well plates.…”

NF-κB and Nrf2 as prime molecular targets for chemoprevention and cytoprotection with anti-inflammatory and antioxidant phytochemicals

“…The green tea polyphenol EGCG also inhibited activation of NF-jB and AP-1 thereby suppressing the COX-2 induction in mouse skin in vivo and/or cultured human mammary epithelial (MCF10A) cells [23]. EGCG also upregulated antioxidant enzymes by activating the Nrf2-ARE signaling pathway [24,25].…”

Efeito anti-inflamatório do gengibre e possível via de sinalização

“…Aplicação tópica de o-tetradecanoyforbol-13-acetato (TPA) pode induzir aumento da expressão de COX-2 (CHUN et al, 2003;KUNDU et al, 2003). Kim e colaboradores em 2005 demonstraram que o pré-tratamento tópico com 6-gingerol em pele de camundongos parece diminuir os níveis de COX-2 induzida pelo TPA, mas sem efeitos sobre a COX-1.…”