Document Detail

Differential effects of selective cyclooxygenase-2 inhibitors in inhibiting proliferation and induction of apoptosis in oral squamous cell carcinoma.
MedLine Citation:
PMID:  18202791     Owner:  NLM     Status:  MEDLINE    
Cyclooxygenase-2 (COX-2), an enzyme that catalyzes the synthesis of prostaglandins, is made inducible by various stimuli such as inflammation. Although COX-2 is commonly overexpressed in a variety of premalignant and malignant conditions including oral leukoplakia and squamous cell carcinoma, relatively little research has compared the effects of various COX-2 inhibitors (celecoxib, NS-398, nimesulide and meloxicam). Therefore, we investigated the effects of four different selective COX-2 inhibitors on the growth of KB cells, derived from oral squamous cell carcinoma (OSCC) and its mechanisms. Celecoxib and NS-398 strongly suppressed the proliferation of KB cells at 10-100 microM, whereas nimesulide and meloxicam are less potent proliferation inhibitors. Only celecoxib induced apoptosis of the KB cells, as detected on the basis of DNA fragmentation, caspase-3/7 activation and cleaved poly(ADP-ribose) polymerase (PARP) fragmentation. All four COX-2 inhibitors increased COX-2 protein expression but suppressed prostaglandin (PG) E2 production in the KB cells, suggesting that the pro-apoptotic effect of celecoxib was unrelated to the inhibition of COX-2. Mechanistically, a high level of p53 protein and a low level of multidrug-resistant protein 1 (MRP1) and breast cancer resistant protein (BCRP) mRNA in KB cells with celecoxib may explain the differential effect of these selective COX-2 inhibitors in KB cells. Taken together, celecoxib is a good therapeutic candidate for treating OSCC through the suppression of cell proliferation and the induction of apoptosis in a COX-2 independent manner.
Seong-Hee Ko; Geun Jun Choi; Ji Hye Lee; Yoon A Han; Soo-Jeong Lim; So Hee Kim
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  19     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-18     Completed Date:  2008-03-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  425-33     Citation Subset:  IM    
College of Dentistry and Research Institute of Oral Science, Kangnung National University, 120 Gangneung Daehangno, Gangneung-City, Gangwon-Do, Korea.
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MeSH Terms
ATP-Binding Cassette Transporters / genetics,  metabolism
Carcinoma, Squamous Cell / enzymology*
Caspase 3 / metabolism
Caspase 7 / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclooxygenase 2 / analysis,  drug effects*
Cyclooxygenase 2 Inhibitors / pharmacology*
DNA Fragmentation
Dinoprostone / metabolism
Mouth Neoplasms / enzymology*
Multidrug Resistance-Associated Proteins / genetics,  metabolism
Neoplasm Proteins / genetics,  metabolism
Protein Biosynthesis / drug effects
Reg. No./Substance:
0/ABCG2 protein, human; 0/ATP-Binding Cassette Transporters; 0/Cyclooxygenase 2 Inhibitors; 0/Multidrug Resistance-Associated Proteins; 0/Neoplasm Proteins; 0/multidrug resistance-associated protein 1; 363-24-6/Dinoprostone; EC 2; EC protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7

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