title: Inhibitors of cyclooxygenase-2 (COX-2) suppressed the proliferation and differentiation of human leukaemia cell lines.
abstract: Prostaglandins (PG) are known to play important roles in the proliferation and differentiation of leukaemia cells. The effect of the inhibitors of cyclooxygenase-2 (COX-2), a rate-limiting enzyme for the synthesis of PG, on the proliferation and differentiation of leukaemia cell lines was investigated. COX-2 inhibitors, NS-398 and nabumetone, suppressed the proliferation of U-937 and ML-1 cells by inducing a G0/G1 cell-cycle arrest. Cell-cycle arrest induced by these COX-2 inhibitors was not associated with an upregulation of the cyclin-dependent kinase inhibitors. COX-2 inhibitors also inhibited the differentiation of these cells induced by interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and retinoic acid (RA). Treatment with NS-398 did not suppress the levels of PGs produced by these cells. Although COX-2 antisense oligonucleotide showed a similar inhibitory effect on these cells, its inhibitory effect was smaller than that of NS-398. These results suggest that COX-2 inhibitors may suppress the proliferation and differentiation of leukaemia cells both via COX-2-dependent and -independent pathways.
authors.affiliation: Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, 2-1-1, Kitasenzoku, Ota-ku, Tokyo 145-8515, Japan. nico@senzoku.showa-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: R
authors.initials: R
authors.lastname: Kamijo
authors.forename: K
authors.initials: K
authors.lastname: Takizawa
authors.forename: M
authors.initials: M
authors.lastname: Hatori
authors.forename: M
authors.initials: M
authors.lastname: Nagumo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D002074:Butanones / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008565:Membrane Proteins; D000077430:Nabumetone; D009578:Nitrobenzenes / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D020298:U937 Cells / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002074:Butanones; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011453:Prostaglandins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000077430:Nabumetone