Document Detail


Celecoxib but not rofecoxib inhibits the growth of transformed cells in vitro.
MedLine Citation:
PMID:  14734479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Nonsteroidal anti-inflammatory drugs reduce the risk of colorectal cancer. The cyclooxygenase (COX) pathway of arachidonic acid metabolism is an important target for nonsteroidal anti-inflammatory drugs. Increased expression of COX-2 was recently shown to be an important step in the multistep process of colorectal cancer carcinogenesis. The new COX-2-specific inhibitors offer the benefit of cancer protection without the gastrointestinal toxicity reported for the old drugs. The purpose of this study was to compare the growth effects of two specific COX-2 inhibitors, celecoxib (Pfizer, Inc., New York, NY), and rofecoxib (Merck, White House Station, NJ) in normal and transformed enterocytes. EXPERIMENTAL DESIGN: Cultures of normal rat intestinal epithelial cell line, IEC-18, vector control cells, c-K-ras, c-K-ras-bak, and antisense-bak derivatives were treated with different dosages of celecoxib (0-60 micro M) and rofecoxib (0-20 micro M). Cell cycle analysis and apoptosis were assessed by fluorescence-activated cell sorting analysis. Protein expression was assessed by Western blot analysis and caspases 3 and 8 activities by ELISA. RESULTS: Celecoxib inhibited cell growth and induced apoptosis in a time- and dose-dependent manner. IEC18 parental cells were two to four times more resistant to celecoxib than ras, ras-bak, and antisense bak transformed cells that overexpress the COX-2 protein. The induction of apoptosis by celecoxib involved the caspase pathways. Rofecoxib, up to its maximal concentration of 20 micro M, did not inhibit cell growth or induce apoptosis. CONCLUSIONS: Celecoxib may prove to be a very efficient component in the prevention and treatment of gastrointestinal tumors because it inhibits the growth of cancerous cells without affecting the growth of normal cells.
Authors:
Diana Kazanov; Hadas Dvory-Sobol; Marjorie Pick; Eliezer Liberman; Ludmila Strier; Efrat Choen-Noyman; Varda Deutsch; Talya Kunik; Nadir Arber
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  10     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-21     Completed Date:  2004-08-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  267-71     Citation Subset:  IM    
Affiliation:
Department of Cancer Prevention, Tel Aviv Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Caspase 3
Caspase 8
Caspases / metabolism
Cell Cycle / drug effects*
Cell Line, Transformed / drug effects*,  metabolism
Cyclooxygenase Inhibitors / pharmacology
Enterocytes / cytology,  drug effects*,  metabolism
Enzyme-Linked Immunosorbent Assay
Genes, ras / physiology
Lactones / pharmacology*
Pyrazoles
Rats
Sulfonamides / pharmacology*
Sulfones
Chemical
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Lactones; 0/Pyrazoles; 0/Sulfonamides; 0/Sulfones; 0/rofecoxib; 169590-42-5/celecoxib; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Casp8 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases

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


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