Document Detail


Antiproliferative effect of nitrosulindac (NCX 1102), a new nitric oxide-donating non-steroidal anti-inflammatory drug, on human bladder carcinoma cell lines.
MedLine Citation:
PMID:  15026549     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Non-steroidal anti-inflammatory drugs (NSAIDs) are potent antitumoral agents but their side effects limit their clinical use. A novel class of drugs, nitric oxide-donating NSAIDs (NO-NSAIDs), was found to be safer and more active than classical NSAIDs. This study explored the effect of the NO-donating sulindac derivative, NCX 1102, on three human urothelial epithelial carcinoma cell lines (T24, 647V, and 1207) and primary cultures of normal urothelial cells. Cytotoxicity, antiproliferative effect, cell cycle alterations, morphological changes, and apoptosis were investigated after treatment with NCX 1102 in comparison with the native molecule. After treatment, there was a cytotoxic effect (with IC(50) at 48 h of 23.1 micro M on 647V, 19.4 micro M on T24, and 14.5 micro M on 1207) and an antiproliferative effect on all three cell lines with NCX 1102 but not with sulindac. No effect was detected on normal urothelial cells. Flow cytometric analysis showed a differential NCX 1102-induced accumulation of cells in various phases of the cell cycle, depending on cell line and concentration. NCX 1102 induced an occurrence of multinucleated cells in all cell lines and mitotic arrest in 647V and 1207. NCX 1102-treated T24 and 647V cell lines showed a significant difference of apoptotic cell amount when compared to controls. Our results demonstrated a greater antiproliferative potency of NCX 1102 compared to its parent molecule sulindac, and suggested that this new NO-NSAID may have therapeutic impact in the management of bladder cancer.
Authors:
Sandra Huguenin; Francis Vacherot; Laurence Kheuang; Jocelyne Fleury-Feith; Marie-Claude Jaurand; Manlio Bolla; Jean-Pierre Riffaud; Dominique K Chopin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  3     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-17     Completed Date:  2004-11-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  291-8     Citation Subset:  IM    
Affiliation:
Equipe de recherche INSERM E 03-37 Oncogenèse des Tumeurs Respiratoires et Urogénitales, Faculté de Médecine, Créteil, France.
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MeSH Terms
Descriptor/Qualifier:
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antineoplastic Agents / pharmacology*
Apoptosis
Carcinoma / drug therapy*,  metabolism
Cell Division
Cell Line, Tumor
Cell Nucleus / metabolism
Dose-Response Relationship, Drug
Epithelium / pathology
Flow Cytometry
Humans
Inhibitory Concentration 50
Nitric Oxide / metabolism*
Sulindac / analogs & derivatives*,  pharmacology*
Time Factors
Urinary Bladder Neoplasms / drug therapy*,  pathology
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antineoplastic Agents; 0/nitrosulindac; 10102-43-9/Nitric Oxide; 38194-50-2/Sulindac

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


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