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 Academic Article uri icon

Overview

MeSH Major

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • Caffeic Acids
  • Cyclooxygenase Inhibitors
  • Inflammation
  • Isoenzymes
  • Mouth Mucosa
  • Phenylethyl Alcohol
  • Promoter Regions, Genetic
  • Prostaglandin-Endoperoxide Synthases

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 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.

publication date

  • May 15, 1999

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 10344742

Additional Document Info

start page

  • 2347

end page

  • 52

volume

  • 59

number

  • 10