calcimycin and caffeic-acid-phenethyl-ester

We investigated the mechanisms by which caffeic acid phenethyl ester (CAPE), a phenolic antioxidant, inhibited the stimulation of prostaglandin (PG) synthesis in cultured human oral epithelial cells and in an animal model of acute inflammation. Treatment of cells with CAPE (2.5 microg/ml) suppressed phorbol ester (12-O-tetradecanoylphorbol-13-acetate; TPA) and calcium ionophore (A23187)-mediated induction of PGE2 synthesis. This relatively low concentration 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 acid from membrane phospholipids was also suppressed by CAPE (4-8 microg/ml). Higher concentrations of CAPE (10-20 microg/ml) suppressed the induction of COX-2 mRNA and protein mediated by TPA. Transient transfections using human COX-2 promoter deletion constructs were performed; the effects of TPA and CAPE were localized to a 124-bp region of the COX-2 promoter. In the rat carrageenan air pouch model of inflammation, CAPE (10-100 mg/kg) caused dose-dependent suppression of PG synthesis. Amounts of COX-2 in the pouch were markedly suppressed by 100 mg/kg CAPE but were unaffected by indomethacin. These data are important for understanding the anticancer and anti-inflammatory properties of CAPE.

Topics: Air; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Arachidonic Acids; Caffeic Acids; Calcimycin; Carcinoma, Squamous Cell; Carrageenan; Cell Membrane; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Enzyme Activation; Enzyme Induction; Epithelial Cells; Genetic Vectors; Humans; Indomethacin; Inflammation; Ionophores; Isoenzymes; Male; Membrane Lipids; Membrane Proteins; Mouth Mucosa; Nucleopolyhedroviruses; Phenylethyl Alcohol; Phospholipids; Promoter Regions, Genetic; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred Lew; Recombinant Fusion Proteins; Tetradecanoylphorbol Acetate; Transfection; Tumor Cells, Cultured