A Simple Approach to Cancer Therapy Afforded by Multivalent Pseudopeptides That Target Cell-Surface Nucleoproteins

作者：Destouches Damien; Page Nicolas; Hamma Kourbali Yamina; Machi Valerie; Chaloin Olivier; Frechault Sophie; Birmpas Charalampos; Katsoris Panagiotis; Beyrath Julien; Albanese Patricia; Maurer Marie; Carpentier Gilles; Strub Jean Marc; Van Dorsselaer Alain; Muller Sylviane; Bagnard Dominique; Briand Jean Paul; Courty Jose^*

来源：Cancer Research, 2011, 71(9): 3296-3305.

DOI：10.1158/0008-5472.CAN-10-3459

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. Cancer Res; 71(9); 3296-305.

• 出版日期2011-5-1