*3.3. COX-2*

Cyclooxygenase-2 (COX-2) is involved in the modulation of different cell processes, such as oxidative stress and inflammation. COX-2 interaction was considered to be part of the mechanism since EGCG was associated with cell cycle modulation and cell death induction in different cancer models. Dysregulated activity of COX-2 were described in many cancers and pathologic conditions. EGCG was demonstrated to inhibit COX-2 both in terms of transcription and translation in human prostate carcinoma cells (androgen-sensitive LNCaP and androgen-insensitive PC-3), without interfering with COX-1 regulation, and this is an important issue in cancer research. These findings point to the use of EGCG >10 μM in the treatment or prevention of prostate cancer [67]. Furthermore, the EGCG inhibition of COX-2 was investigated on a colon cancer model, in which a significant decrease of COX-2 activity in the cells of the colon of rats treated with green tea extract pointing to a prevention in the formation of preneoplastic foci [68]. The authors fed the animals with freshly prepared an aqueous solution of green tea extract, reconstituted from the lyophilisate, at a concentration of 0.02% (wt/vol) in which EGCG was at 14% dry weight. COX-2 inhibition was also studied on the potential antitumor activity of EGCG in skin cancer [69]. EGCG was administred to mice by gavage at a dose of either 20 or 50 mg/kg body weight 1 h before topical application of the tumor promoter 12- *O*-tetradecanoylphorbol-13-acetate to the shaved back. In this paper, the inhibitor mechanism of COX-2 by EGCG was described as the cascade e ffect of EGCG inhibition of the catalytic activity of ERK and p38 MAPK that are the upstream enzymes that regulate COX-2 expression [69]. From another point of view, the interaction between EGCG and COX-2 were investigated in arthritis. A solution of 0.2% green tea polyphenols in the water was prepared and given *ad libitum* (the sole source of drinking water for mice). Treatment with this preparation in a collagen II-induced arthritis mouse model demonstrated to reduce the pathological picture of arthritis, with decrease of TNFα, IFN-γ, and Cox-2 especially in mice arthritic joints [70]. Thus, it was demonstrated that the treatment of human chondrocytes with EGCG at concentration >100 μM was related to the inhibition of COX-2 and iNOS activity indicating a possible involvement of this treatment in the inhibition of cartilage resorption in arthritis [71].
