Exp Mol Med.  2006 Jun;38(3):203-209.

Heterogeneous nuclear ribonuclear protein C is increased in the celecoxib-induced growth inhibition of human oral squamous cell carcinoma

• Lee EJ
• Kim SH
• Kwark YE
• Kim J

Abstract

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-10B, which was established to be used as in vitro OSCC model, and identified celecoxib-regulated protein by proteomics techniques. Celecoxib (IC50=37 micrometer) inhibited the growth of YD-10B cells with the decrease of COX-2 protein expression. Its inhibition could be linked in the arrest of G1 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-10B 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-10B cells. In addition, YD-10B cells could be useful to study the pathological mechanism of OSCC.

Keyword

carcinoma, squamous cell; celecoxib; cell cycle; cyclin-dependent kinase inhibitor p27; cyclooxygenase 2 inhibitors; heterogeneous-nuclear ribonucleoprotein C

MeSH Terms

Tumor Cells, Cultured
Tongue Neoplasms/metabolism/pathology
Sulfonamides/*pharmacology
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Pyrazoles/*pharmacology
Proteomics/methods
Male
Immunoblotting
Humans
Heterogeneous-Nuclear Ribonucleoprotein Group C/analysis/*metabolism
Electrophoresis, Gel, Two-Dimensional
Cyclooxygenase Inhibitors/pharmacology
Cyclooxygenase 2/metabolism
Cyclin-Dependent Kinase Inhibitor p27/analysis/metabolism
Cell Survival/drug effects
Cell Proliferation/*drug effects
Cell Line, Tumor
Cell Cycle/drug effects
Carcinoma, Squamous Cell/metabolism/pathology
Aged
Actins/metabolism