A selective cyclooxygenase-2 inhibitor, NS398, inhibits cell growth and induces cell cycle arrest in the G2/M phase in human esophageal squamous cell carcinoma cells.
It is well known that cyclooxygenase (COX) -2 is expressed in a variety of human malignant solid tumors, associated with tumor angiogenesis, cell proliferation and inhibition of apoptosis. Here, we examined the effect of NS398, a selective COX-2 inhibitor, on two human esophageal squamous cell carcinoma (SCC) cell lines, TE-1 and TE-12. Western blot analysis confirmed the expression of COX-2 in TE-12, but not in TE-1. Treatment with 100microM NS398 suppressed the cell viability in TE-12 (48.6% of control) after 48 hours, in contrast to showing no effects in TE-1. The apoptotic index was extremely low in both cell lines after the treatment. NS398 clearly increased the number of cells in the G2/M phase and decreased the cells in the G1 and S phases in TE-12, but not TE-1. A pre-G1 fraction was not noted in either cell line. Moreover, TE-12 cells showed a decrease in the expression levels of cyclin B1 and an increase in p27Kip1. These findings suggest that NS398 inhibits cell growth and induces G2/M arrest in human SCC cells expressing COX-2.
Kase
S
S
Dept of Microbiology and Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Osaki
M
M
Honjo
S
S
Takeda
A
A
Adachi
K
K
Araki
K
K
Ito
H
H
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C534699:CCNB1 protein, human; C436291:CDKN1B protein, human; D002352:Carrier Proteins; D019926:Cyclin B; D056744:Cyclin B1; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases