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 Journal Article
| Authors: | Michaluart, P.; Masferrer, J. L.; Carothers, A. M.; Subbaramaiah, K.; Zweifel, B. S.; Koboldt, C.; Mestre, J. R.; Grunberger, D.; Sacks, P. G.; Tanabe, T.; Dannenberg, A. J. |
| Article Title: | 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 |
| Abstract: | 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 μg/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 μg/ml). Higher concentrations of CAPE (10-20 μg/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-hp 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. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; promoter region; gene deletion; carcinoma, squamous cell; nonhuman; animals; animal experiment; animal model; inflammation; membrane proteins; enzyme activation; tumor cells, cultured; enzyme activity; transfection; genetic vectors; recombinant fusion proteins; drug mechanism; cell culture; cyclooxygenase 2 inhibitors; cyclooxygenase 2; indometacin; anti-inflammatory agents, non-steroidal; anticarcinogenic agents; cyclooxygenase 1; rat; cell membrane; plasmid; immunoblotting; epithelial cells; rats; arachidonic acid; mouth mucosa; enzyme assay; concentration response; isoenzymes; enzyme induction; rats, inbred lew; phospholipids; tetradecanoylphorbol acetate; prostaglandin synthesis; dinoprostone; membrane lipids; caffeic acid; air; carrageenan; ionophores; promoter regions (genetics); indomethacin; prostaglandin-endoperoxide synthases; caffeic acids; cyclooxygenase inhibitors; caffeic acid phenethyl ester; humans; human; male; priority journal; article; arachidonic acids; calcimycin; prostaglandin release; nucleopolyhedrovirus; phenylethyl alcohol |
| Journal Title: | Cancer Research |
| Volume: | 59 |
| Issue: | 10 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1999-05-15 |
| Start Page: | 2347 |
| End Page: | 2352 |
| Language: | English |
| PUBMED: | 10344742 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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