A selective cyclooxygenase-2 inhibitor, NS-398, inhibits cell growth by cell cycle arrest in a human malignant fibrous histiocytoma cell line.
BACKGROUND
NS-398, a selective cyclooxygenase-2 (COX-2) inhibitor, has been shown to suppress cell proliferation and induce apoptosis in a variety of human cancer cell lines in vitro, except for sarcoma cell lines. The aim of this study was to examine the effect of NS-398 on two human malignant fibrous histiocytoma (MFH) cell lines: MFH-ino and MFH-ToE.


METHODS
We investigated the effect of NS-398 at various concentrations on the growth of MFH cell lines using cell proliferation assay, cell cycle analysis and EIA assay of PGE2 production.


RESULTS
Western blot analysis revealed COX-2 protein expression in both MFH cell lines. NS-398 at 10 or 100 microM resulted in inhibition of the cell proliferation in a dose- and time-dependent manner. NS-398 at 100 microM also induced G0/G1 arrest accompanied by up-regulation of P21WAF1 in MFH-ino cells in a time-dependent manner until 72 hours. NS-398 slightly increased the number of cells in the G2/M-phase and decreased the number in the G0/G1-phase in MFH-ToE cells lacking p53 gene function. Moreover, NS-398 down-regulated PGE2 production in the MFH-ToE cells in a time-dependent manner, but not in the MFH-ino cells.


CONCLUSIONS
Our results indicate that NS-398 inhibits the cell growth and induces G0/G1 arrest in MFH-ino cells accompanied with up-regulation of P21WAF1.
Yamashita
Hideki
H
Division of Organ Pathology Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan. hidekiy@grape.med.tottori-u.ac.jp
Osaki
Mitsuhiko
M
Honjo
Soichiro
S
Yoshida
Haruhiko
H
Teshima
Ryota
R
Ito
Hisao
H
D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018219:Histiocytoma, Benign Fibrous / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000633:toxicity*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D013449:Sulfonamides / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases