Inhibition of cyclooxygenase-2 expression. An approach to preventing head and neck cancer.
Cyclooxygenase (COX) catalyzes the formation of prostaglandins (PG) from arachidonic acid. A large body of evidence has accumulated to suggest that COX-2, the inducible form of COX, is important in carcinogenesis. In this study, we determined whether (1) COX-2 was overexpressed in squamous cell carcinoma of the head and neck (HNSCC) and whether (2) retinoids, a class of chemopreventive agents, blocked epidermal growth factor (EGF)-mediated activation of COX-2 expression. Levels of COX-2 mRNA were determined in 15 cases of HNSCC and 10 cases of normal oral mucosa. Nearly a 100-fold increase in amounts of COX-2 mRNA was detected in HNSCC. By immunoblot analysis, COX-2 protein was detected in 6 of 6 cases of HNSCC but was undetectable in normal mucosa. Because retinoids protect against oral cavity cancer, we investigated whether retinoids could suppress EGF-mediated induction of COX-2 in cultured oral squamous carcinoma cells. Treatment with EGF led to increased levels of COX-2 mRNA, COX-2 protein, and synthesis of PG. These effects were suppressed by a variety of retinoids. Based on the results of this study, it will be important to establish whether newly developed selective COX-2 inhibitors are useful in preventing or treating HNSCC. Moreover, the anticancer properties of retinoids may be due, in part, to inhibition of COX-2 expression. Combining a retinoid with a selective COX-2 inhibitor may be more effective than either agent alone in preventing cancer of the upper aerodigestive tract.
Mestre
J R
JR
Anne Fisher Nutrition Center, Strang Cancer Prevention Center, New York, New York, USA.
Chan
G
G
Zhang
F
F
Yang
E K
EK
Sacks
P G
PG
Boyle
J O
JO
Shah
J P
JP
Edelstein
D
D
Subbaramaiah
K
K
Dannenberg
A J
AJ
D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000517:prevention & control*; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000517:prevention & control*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000494:pharmacology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000494:pharmacology*; D012176:Retinoids / Q000494:pharmacology* / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D012176:Retinoids; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases