Document Detail


Selective cyclooxygenase-2 inhibitors inhibit growth and induce apoptosis of bladder cancer.
MedLine Citation:
PMID:  16391871     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Selective COX-2 inhibitors such as celecoxib and NS-398 are being evaluated as chemopreventive and therapeutic agents for bladder and other cancers. We investigated the effects of these nonsteroidal anti-inflammatory agents on a panel of bladder cancer cell lines, and assessed their effects on anchorage-dependent and -independent growth, cell cycle, apoptosis and morphology. The human bladder cancer cell lines UM-UC-1, -3, and -6 were assayed for COX-2 expression by Western analysis using a monoclonal antibody to COX-2. UM-UC-1, -3, and -6 cells were grown in the presence of increasing concentrations of NS-398 and celecoxib, and cell growth was quantitated over 7 days by crystal violet elution. The cell lines were treated with NS-398 and celecoxib for 48 h and analyzed by flow cytometry with propidium iodide staining and Br-dUTP staining for apoptosis. Anchorage-independent growth was assessed using an agarose growth assay. Western analysis demonstrated that COX-2 expression in UM-UC-1, -6, and -3 was high, low, and undetectable, respectively. NS-398 and celecoxib produced dose-dependent growth inhibition of UM-UC-1 and -6. Both NS-398 and celecoxib also inhibited anchorage-dependent and -independent growth of UM-UC-3 in a dose-dependent fashion, despite the low basal expression of COX-2 in this cell line. Cell cycle analyses of UM-UC-1 and -6 revealed a 50% reduction in S-phase in the presence of 100 microM NS-398 whereas a smaller reduction in S-phase was noted in UM-UC-3 cells. Furthermore, treatment with 100 microM celecoxib resulted in significant apoptosis in all three cell lines, which was associated with downregulation of Bcl-2. COX-2 selective inhibitors NS-398 and celecoxib produced dose-dependent growth inhibition of bladder cancer cells associated with a significant reduction in S-phase. Induction of apoptosis in all three cell lines by celecoxib was associated with downregulation of Bcl-2. These changes occur independently of COX-2 expression levels suggesting the presence of a COX-2 independent pathway.
Authors:
Jason Gee; I-Ling Lee; David Jendiroba; Susan M Fischer; H Barton Grossman; Anita L Sabichi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  15     ISSN:  1021-335X     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-04     Completed Date:  2006-06-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  471-7     Citation Subset:  IM    
Affiliation:
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. gee@surgery.wisc.edu
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Blotting, Western
Carcinoma, Transitional Cell / drug therapy*
Cell Line, Tumor
Cell Proliferation / drug effects*
Cyclooxygenase 2 / drug effects,  metabolism
Cyclooxygenase 2 Inhibitors / pharmacology*
Dose-Response Relationship, Drug
Down-Regulation
Flow Cytometry
Humans
Nitrobenzenes / pharmacology
Proto-Oncogene Proteins c-bcl-2 / drug effects,  metabolism
Pyrazoles / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Sulfonamides / pharmacology
Urinary Bladder Neoplasms / drug therapy*
Chemical
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Nitrobenzenes; 0/Proto-Oncogene Proteins c-bcl-2; 0/Pyrazoles; 0/Sulfonamides; 123653-11-2/N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; 169590-42-5/celecoxib; EC 1.14.99.1/Cyclooxygenase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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