Elevated expression of cyclooxygenase (COX)-2 in oral squamous cell carcinoma--evidence for COX-2 induction by areca quid ingredients in oral keratinocytes

J Oral Pathol Med. 2003 Oct;32(9):522-9. doi: 10.1034/j.1600-0714.2003.00182.x.

Abstract

Background: Elevated expression of cyclooxygenase (COX)-2 has been demonstrated in several human cancers. Whether COX-2 is up-regulated in areca quid (AQ) related oral squamous cell carcinoma (OSCC) is unknown and the potential of AQ ingredients to induce COX-2 expression has not been studied.

Methods: COX-2 expression was analyzed by immunohistochemistry and RT-PCR in oral tissues. The COX-2 mRNA and protein induction potential of AQ ingredients were analyzed by real-time RT-PCR and Western blotting in normal human oral keratinocyte (NHOK).

Results: COX-2 protein expression was significantly higher (P < 0.01) in OSCC (n = 27) as compared to their adjacent non-cancerous matched tissue (NCMT). COX-2 protein was nearly undetectable in control normal oral mucosa. The level of COX-2 mRNA was markedly elevated in 63% (12/19) of OSCC compared to NCMT. Hydroxychavicol induced COX-2 mRNA and protein expression in NHOK.

Conclusions: COX-2 protein as well as mRNA expression were significantly enhanced in OSCC as compared to NCMT. Hydroxychavicol, a unique ingredient in AQ, induced COX-2 expression in NHOK, which highlighted early involvement of COX-2 in AQ-associated oral oncogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Areca*
  • Carcinoma, Squamous Cell / enzymology*
  • Case-Control Studies
  • Chi-Square Distribution
  • Cyclooxygenase 2
  • Dinoprostone / analysis
  • Dinoprostone / biosynthesis
  • Enzyme Induction
  • Eugenol / analogs & derivatives*
  • Eugenol / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Isoenzymes / analysis*
  • Isoenzymes / biosynthesis
  • Keratinocytes / enzymology*
  • Membrane Proteins
  • Mouth Mucosa / enzymology
  • Mouth Neoplasms / enzymology*
  • Peroxidases / analysis*
  • Peroxidases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / analysis*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Tumor Cells, Cultured

Substances

  • Isoenzymes
  • Membrane Proteins
  • 2-hydroxychavicol
  • Eugenol
  • Peroxidases
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone