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.