A simple approach to cancer therapy afforded by multivalent pseudopeptides that target cell-surface nucleoproteins.
Fiche publication
Date publication
mai 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BAGNARD Dominique, Dr VAN DORSSELAER Alain
Tous les auteurs :
Destouches D, Page N, Hamma-Kourbali Y, Machi V, Chaloin O, Frechault S, Birmpas C, Katsoris P, Beyrath J, Albanese P, Maurer M, Carpentier G, Strub JM, Van Dorsselaer A, Muller S, Bagnard D, Briand JP, Courty J
Lien Pubmed
Résumé
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.
Référence
Cancer Res. 2011 May 1;71(9):3296-305