In vitro and in vivo evaluation of NCX 4040 cytotoxic activity in human colon cancer cell lines

摘要: Nitric oxide-releasing nonsteroidal antiinflammatory drugs (NO-NSAIDs) are reported to be safer than NSAIDs because of their lower gastric toxicity. We compared the effect a novel NO-releasing derivate, NCX 4040, with that aspirin and its denitrated analog, 4042, in vitro vivo human colon cancer models investigated mechanisms action underlying antitumor activity. In cytotoxicity was evaluated on panel lines (LoVo, LoVo Dx, WiDr LRWZ) by sulforhodamine B assay. Cell cycle perturbations apoptosis were flow cytometry. Protein expression detected Western blot. experiments, tumor-bearing mice treated five times week, for six consecutive weeks. studies, 4042 did not induce an any cell lines, whereas 4040 produced marked cytostatic dose-related effect, indicating pivotal role -NO2 group. Furthermore, LRWZ we observed caspase-9 -3-mediated apoptosis, no apoptotic after drug exposure or Dx lines. both parental compound administered per os. induced 40% reduction tumor weight. Conversely, influence growth at all. but compound, aspirin, showed antiproliferative activity, potential usefulness treat cancer.