title: A simple approach to cancer therapy afforded by multivalent pseudopeptides that target cell-surface nucleoproteins.
abstract: 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.
authors.affiliation: Université Paris-Est, Créteil, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Destouches
authors.forename: Nicolas
authors.initials: N
authors.lastname: Page
authors.forename: Yamina
authors.initials: Y
authors.lastname: Hamma-Kourbali
authors.forename: Valérie
authors.initials: V
authors.lastname: Machi
authors.forename: Olivier
authors.initials: O
authors.lastname: Chaloin
authors.forename: Sophie
authors.initials: S
authors.lastname: Frechault
authors.forename: Charalampos
authors.initials: C
authors.lastname: Birmpas
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Katsoris
authors.forename: Julien
authors.initials: J
authors.lastname: Beyrath
authors.forename: Patricia
authors.initials: P
authors.lastname: Albanese
authors.forename: Marie
authors.initials: M
authors.lastname: Maurer
authors.forename: Gilles
authors.initials: G
authors.lastname: Carpentier
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Strub
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Dominique
authors.initials: D
authors.lastname: Bagnard
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Briand
authors.forename: José
authors.initials: J
authors.lastname: Courty
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays; D000097796:Nucleolin
chemical_list: D008024:Ligands; D010455:Peptides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C580583:N6L peptide