| Summary: | <p>Abstract</p> <p>Background</p> <p>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 of a novel NO-releasing derivate, NCX 4040, with that of aspirin and its denitrated analog, NCX 4042, in <it>in vitro </it>and <it>in vivo </it>human colon cancer models and investigated the mechanisms of action underlying its antitumor activity.</p> <p>Methods</p> <p><it>In vitro </it>cytotoxicity was evaluated on a panel of colon cancer lines (LoVo, LoVo Dx, WiDr and LRWZ) by sulforhodamine B assay. Cell cycle perturbations and apoptosis were evaluated by flow cytometry. Protein expression was detected by Western blot. In the <it>in vivo </it>experiments, tumor-bearing mice were treated with NCX 4040, five times a week, for six consecutive weeks.</p> <p>Results</p> <p>In the <it>in vitro </it>studies, aspirin and NCX 4042 did not induce an effect on any of the cell lines, whereas NCX 4040 produced a marked cytostatic dose-related effect, indicating a pivotal role of the -NO<sub>2 </sub>group. Furthermore, in LoVo and LRWZ cell lines, we observed caspase-9 and -3-mediated apoptosis, whereas no apoptotic effect was observed after drug exposure in WiDr or LoVo Dx cell lines. In <it>in vivo </it>studies, both NCX 4040 and its parental compound were administered <it>per os</it>. NCX 4040 induced a 40% reduction in tumor weight. Conversely, aspirin did not influence tumor growth at all.</p> <p>Conclusions</p> <p>NCX 4040, but not its parental compound, aspirin, showed an <it>in vitro </it>and <it>in vivo </it>antiproliferative activity, indicating its potential usefulness to treat colon cancer.</p>
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