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

Pedro Michaluart, Jaime L. Masferrer, Adelaide M. Carothers, Kotha Subbaramaiah, Ben S. Zweifel, Carol Koboldt, Juan R. Mestre, Dezider Grunberger, Peter G. Sacks, Tadashi Tanabe, Andrew J. Dannenberg

Research output: Contribution to journalArticle

328 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2347-2352
Number of pages6
JournalCancer research
Volume59
Issue number10
StatePublished - May 15 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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