A simple approach to cancer therapy afforded by multivalent pseudopeptides that target cell-surface nucleoproteins
SourceCancer Research, 71, 9, (2011), pp. 3296-305
Article / Letter to editor
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Paediatrics - OUD tm 2017
SubjectIGMD 8: Mitochondrial medicine NCMLS 5: Membrane transport and intracellular motility; NCMLS 5: Membrane transport and intracellular motility
Recent studies have implicated the involvement of cell surface forms of nucleolin in tumor growth. In this study, we investigated whether a synthetic ligand of cell-surface nucleolin known as N6L could exert antitumor activity. We found that N6L inhibits the anchorage-dependent and independent growth of tumor cell lines and that it also hampers angiogenesis. Additionally, we found that N6L is a proapoptotic molecule that increases Annexin V staining and caspase-3/7 activity in vitro and DNA fragmentation in vivo. Through affinity isolation experiments and mass-spectrometry analysis, we also identified nucleophosmin as a new N6L target. Notably, in mouse xenograft models, N6L administration inhibited human tumor growth. Biodistribution studies carried out in tumor-bearing mice indicated that following administration N6L rapidly localizes to tumor tissue, consistent with its observed antitumor effects. Our findings define N6L as a novel anticancer drug candidate warranting further investigation.
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