Targeted inhibition of NMYC by peptide nucleic acid in N-myc amplified human neuroblastoma cells: cell-cycle inhibition with induction of neuronal cell differentiation and apoptosis

• DOI: 10.3892/ijo.24.2.265
• Publication Date: 2014-03-10T07:29:31Z
• Authors: Andrea Pession; Roberto Tonelli; Raffaele Fronza; Elena Sciamanna; Roberto Corradini; Stefano Sforza; Tullia Tedeschi; Rosangela Marchelli; Lorenzo Montanaro; Consuelo Camerin; Monica Franzoni; Guido Paolucci
• Keywords: Peptide nucleic acid

We developed an antisense peptide nucleic acid (PNA) targeted against a unique sequence in the terminus of 5'-UTR N-myc, designed for selective inhibition NMYC neuroblastoma cells. Fluorescent microscopy showed carrier-free delivery PNA to two human neuro-blastoma cell lines: GI-LI-N (N-myc-amplified) and GI-CA-N (N-myc-unamplified). Only former, treatment determined 70% cell-viability reduction (at 48 h). In N-myc-amplified cells, NMYC-translation (Western blotting), accumulation cells G1, induction differentiation apoptosis. Selectivity was demonstrated by altering three point mutations. These findings should encourage development PNA-based tumor-specific agent (or other neoplasms) with N-myc overexpression.