Nitrosulindac (NCX 1102): a new nitric oxide-donating non-steroidal anti-inflammatory drug (NO-NSAID), inhibits proliferation and induces apoptosis in human prostatic epithelial cell lines.
BACKGROUND
The aim of our study was to explore the anti-tumoral potential of the Nitric Oxide-Donating Non-Steroidal Anti-Inflammatory Drugs (NO-NSAID) NCX1102 (nitrosulindac), on three human prostatic epithelial cell lines at varying degree of transformation (PNT1A, LNCaP, and PC3).


METHODS
Cytotoxicity, anti-proliferative effects, cell-cycle alterations, morphological changes, and apoptosis were investigated after treatment with nitrosulindac in comparison to the native molecule sulindac. Involvement of the polyamine pathway in the action of nitrosulindac was also examined.


RESULTS
Nitrosulindac but not sulindac exerted a cytotoxic effect on all cell lines and an anti-proliferative effect on LNCaP and PC3 cells only. Nitrosulindac differentially altered the cell cycle, induced mitotic arrest and displayed a pro-apoptotic activity in all cell lines. Finally, the polyamine pathway does not seem to be involved in the mechanism of nitrosulindac action.


CONCLUSIONS
Our results demonstrate the anti-proliferative and proapoptotic activity of nitrosulindac on prostate cancer cell lines and suggest its potential interest for new strategies in the management of prostate cancer.
Equipe de recherche INSERM E 03-37 Oncogenèse des Tumeurs Respiratoires et Urogénitales, Faculté de Médecine, Rue du Général Sarrail, Créteil, Cedex, France.
Sandra
S
Huguenin
Jocelyne
J
Fleury-Feith
Laurence
L
Kheuang
Marie-Claude
MC
Jaurand
Manlio
M
Bolla
Jean-Pierre
JP
Riffaud
Dominique K
DK
Chopin
Francis
F
Vacherot
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D013467:Sulindac / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C431582:nitrosulindac; D013467:Sulindac; D009569:Nitric Oxide