Inhibitor of cyclooxygenase-2 induces cell-cycle arrest in the epithelial cancer cell line via up-regulation of cyclin dependent kinase inhibitor p21
| Autor: | Takahiko Toyoshima, Daisuke Ito, Ryutaro Kamijo, Masao Nagumo, Kunio Takizawa, Kaname Sumitani |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
squamous cell carcinoma Programmed cell death Cancer Research Blotting Western Apoptosis Biology NS-398 Transfection G0/G1 arrest Polymerase Chain Reaction Cyclin-dependent kinase Cyclins Tumor Cells Cultured Humans Cyclooxygenase Inhibitors Experimental Therapeutics Nitrobenzenes DNA Primers Sulfonamides Cyclooxygenase 2 Inhibitors p21 Cell Cycle Cell Membrane Membrane Proteins G0 phase Cell cycle Oligonucleotides Antisense Tongue Neoplasms Up-Regulation Gene Expression Regulation Neoplastic Isoenzymes Epidermoid carcinoma Oncology Cell culture Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases cyclooxygenase-2 Cancer research biology.protein Carcinoma Squamous Cell Prostaglandins |
| Zdroj: | British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | Cyclooxygenase-2 is the rate-limiting enzyme in synthesis of prostaglandins and other eicosanoids. Prior reports have shown that inhibition of cyclooxygenase-2 activity, either by selective inhibitors or by antisense oligonucleotide, results in suppression of growth of squamous cell carcinoma cell lines which express high cyclooxygenase-2 levels, such as NA, a cell line established from a squamous cell carcinoma of the tongue. To investigate the mechanisms by which cyclooxygenase-2 inhibitors suppressed growth of these cells, the effects of NS-398, the selective cyclooxygenase-2 inhibitor, on cell-cycle distribution were examined. NS-398 induced G0/G1 cell-cycle arrest in NA cells which expressed cyclooxygenase-2. G0/G1 arrest induced by NS-398 was accompanied by up-regulation of cyclin-dependent kinase inhibitor p21, but not by up-regulation of the other cyclin-dependent kinase inhibitors. Transfection with p21 antisense oligonucleotide inhibited cell-cycle arrest induced by NS-398. Accumulation in G0/G1 was also observed in NA cells transfected with cyclooxygenase-2 antisense oligonucleotide. On the other hand, NS-398-treated NA cells showed a loss of plasma membrane asymmetry, a marker of early events in apoptosis. However, NS-398 did not induce other morphological and biochemical changes related to apoptotic cell death. These results suggest that cyclooxygenase-2 inhibitor induces G0/G1 cell-cycle arrest in NA cells by up-regulation of p21. Our results also suggest that NS-398 is not sufficient to complete the whole process of apoptosis in NA cells, although it induces an early event in apoptosis. British Journal of Cancer (2002) 86, 1150–1156. DOI: 10.1038/sj/bjc/6600183 www.bjcancer.com © 2002 Cancer Research UK |
| Databáze: | OpenAIRE |
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