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.

Abstract

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

• 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
• Journal: International journal of oncology (Int J Oncol) Vol. 24 Issue 2 Pg. 265-72 (Feb 2004) ISSN: 1019-6439 [Print] Greece
• PMID: 14719101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Peptide Nucleic Acids
• Proto-Oncogene Proteins c-myc

Topics

• Apoptosis
• Base Sequence
• Blotting, Western
• Cell Cycle
• Cell Differentiation
• Cell Division
• Cell Line, Tumor
• DNA Primers (pharmacology)
• Flow Cytometry
• G1 Phase
• Humans
• Microscopy, Fluorescence
• Molecular Sequence Data
• Neuroblastoma (drug therapy, metabolism)
• Neurons (pathology)
• Peptide Nucleic Acids (therapeutic use)
• Point Mutation
• Proto-Oncogene Proteins c-myc (antagonists & inhibitors, biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction