Elevated expression of cyclooxygenase (COX)-2 in oral squamous cell carcinoma--evidence for COX-2 induction by areca quid ingredients in oral keratinocytes.
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.
Tang
Deh-Wei
DW
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Lin
Shu-Chun
SC
Chang
Kuo-Wei
KW
Chi
Chin-Wen
CW
Chang
Che-Shoa
CS
Liu
Tsung-Yun
TY
D001114:Areca; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis; D004790:Enzyme Induction; D005054:Eugenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000032:analysis* / Q000096:biosynthesis; D015603:Keratinocytes / Q000201:enzymology*; D008565:Membrane Proteins; D009061:Mouth Mucosa / Q000201:enzymology; D009062:Mouth Neoplasms / Q000201:enzymology*; D010544:Peroxidases / Q000032:analysis* / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; C051268:2-hydroxychavicol; D005054:Eugenol; D010544:Peroxidases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone