Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation

We investigated the mechanisms by which caffeic acid phenethyl ester (CAPE) , a phenolic antioxidant, inhibited the stimulation of prostaglandin (PG) s ynthesis in cultured human oral epithelial cells and in an animal model of acute inflammation. Treatment of cells with CAPE (2.5 mu g/ml) suppressed p horbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) and calcium ionoph ore (A23187)-mediated induction of PGE(2) synthesis, This relatively low co ncentration of CAPE did not affect amounts of cyclooxygenase (COX) enzymes. CAPE nonselectively inhibited the activities of baculovirus-expressed hCOX -1 and hCOX-2 enzymes, TPA- and A23187-stimulated release of arachidonic ac id from membrane phospholipids was also suppressed by CAPE (4-8 mu g/ml). H igher concentrations of CAPE (10-20 mu g/ml) suppressed the induction of CO X-2 mRNA and protein mediated by TPA, Transient transfections using human C OX-2 promoter deletion constructs were performed; the effects of TPA and CA PE were localized to a 124-bp region of the COX-2 promoter. In the rat carr ageenan air pouch model of inflammation, CAPE (10-100 mg/kg) caused dose-de pendent suppression of PG synthesis. Amounts of COX-2 in the pouch were mar kedly suppressed by 100 mg/kg CAPE but were unaffected by indomethacin. The se data are important for understanding the anticancer and anti-inflammator y properties of CAPE.