Evaluation of the antitumoral potential of different nitric oxide-donating non-steroidal anti-inflammatory drugs (NO-NSAIDs) on human urological tumor cell lines.
Our work aimed at identifying the antitumoral potential of new nitric oxide (NO)-releasing non-steroidal anti-inflammatory drug (NSAID) derivatives on human prostate and bladder carcinoma cell lines. Among all molecules tested, two sulindac derivatives, NCX 1102 ((Z)-5-fluoro-2-methyl-1-[[4-(methylsulfinyl)phenyl] methylene]-1H-indene-3-acetic acid 4-(nitrooxy)butyl ester) and NCX 1105 ((Z)-5-fluoro-2-methyl-1-[[4-(methylsulfinyl)phenyl] methylene]-1H-indene-3-acetic acid 6-(nitrooxymethyl)-2-methylpyrydyl ester hydrochloride), were the most cytotoxic compounds. In contrast to its parent molecule sulindac, cell cycle analysis showed that NCX 1102 led to cell accumulation in the G2-M transition stage in all cell lines, and induced apoptosis in five out of the six cell lines. Thus, NO-NSAIDs may be useful for the elaboration of new therapeutic strategies in the management of bladder and prostate cancer.
Huguenin
Sandra
S
Groupe de recherche INSERM E 03-37, Oncogenèse des Tumeurs Respiratoires et Urogénitales, Faculté de Médecine, 8, Rue du Général Sarrail, 94010 Créteil Cedex, France.
Vacherot
Francis
F
Fleury-Feith
Jocelyne
J
Riffaud
Jean-Pierre
JP
Chopin
Dominique K
DK
Bolla
Manlio
M
Jaurand
Marie-Claude
MC
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D020030:Nitric Oxide Donors