Heterogeneous nuclear ribonuclear protein C is increased in the celecoxib-induced growth inhibition of human oral squamous cell carcinoma.
Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) that is a critical factor in carcinogenesis, but precise mechanism of its action remains to be elucidated. Here we evaluated the inhibitory effect of celecoxib on cell growth of human oral squamous cell carcinoma (OSCC) YD-10(B), which was established to be used as in vitro OSCC model, and identified celecoxib-regulated protein by proteomics techniques. Celecoxib (IC(50)=37 microM) inhibited the growth of YD-10(B) cells with the decrease of COX-2 protein expression. Its inhibition could be linked in the arrest of G(1) phase with increased levels of p(27) protein, a specific CDK inhibitor. Using proteomics, the 10- to 20-fold increase of heterogeneous nuclear ribonuclear protein C (hnRNP C), which has been suggested to be related with the translation of p(27) mRNA, was observed in celecoxib-treated YD-10(B) cells. In summary, celecoxib has a potential to induce the protein expression of hnRNP C and its increase subsequently induce the translation of p(27) mRNA, which trigger the inhibition of cell growth via p(27)-regulated cell cycle arrest in YD-10(B) cells. In addition, YD-10(B) cells could be useful to study the pathological mechanism of OSCC.
Lee
Eun Ju
EJ
Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 120-752, Korea.
Kim
Seong Hwan
SH
Kwark
Young Eun
YE
Kim
Jin
J
D000199:Actins / Q000378:metabolism; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D000068579:Celecoxib; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D040901:Proteomics / Q000379:methods; D011720:Pyrazoles / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013449:Sulfonamides / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
D000199:Actins; D016861:Cyclooxygenase Inhibitors; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D011720:Pyrazoles; D013449:Sulfonamides; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051546:Cyclooxygenase 2; D000068579:Celecoxib