title: Myc Decoy Oligodeoxynucleotide Inhibits Growth and Modulates Differentiation of Mouse Embryonic Stem Cells as a Model of Cancer Stem Cells.
abstract: Myc (c-Myc) alone activates the embryonic stem cell-like transcriptional module in both normal and transformed cells. Its dysregulation might lead to increased cancer stem cells (CSCs) population in some tumor cells.
  
  
  
  In order to investigate the potential of Myc decoy oligodeoxynucleotides for differentiation therapy, mouse embryonic stem cells (mESCs) were used in this study as a model of CSCs. To our best of knowledge this is the first report outlining the application of Myc decoy in transcription factor decoy "TFD" strategy for inducing differentiation in mESCs.
  
  
  
  A 20-mer double-stranded Myc transcription factor decoy and scrambled oligodeoxynucleotides (ODNs) were designed, analyzed by electrophoretic mobility shift (EMSA) assay and transfected into the mESCs under 2 inhibitors (2i) condition. Further investigations were carried out using fluorescence and confocal microscopy, cell proliferation and apoptosis analysis, alkaline phosphatase and embryoid body formation assay, real-time PCR and western blotting.
  
  
  
  EMSA data showed that Myc decoy ODNs bound specifically to c-Myc protein. They were found to be localized in both cytoplasm and nucleus of mESCs. Our results revealed the potential capability of Myc decoy ODNs to decrease cell viability by (16.1±2%), to increase the number of cells arrested in G0/G1 phases and apoptosis by (14.2±3.1%) and (12.1±3.2%), respectively regarding the controls. Myc decoy could also modulate differentiation in mESCs despite the presence of 2i/LIF in our medium the presence of 2i/LIF in our medium.
  
  
  
  The optimized Myc decoy ODNs approach might be considered as a promising alternative strategy for differentiation therapy investigations.
authors.affiliation: Biochemistry Department, Pasteur Institute of Iran, Tehran. Iran.
authors.forename: Behrooz
authors.initials: B
authors.lastname: Johari
authors.affiliation: Biochemistry Department, Pasteur Institute of Iran, Tehran. Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Ebrahimi-Rad
authors.affiliation: Biochemistry Department, Pasteur Institute of Iran, Tehran. Iran.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Maghsood
authors.affiliation: Biochemistry Department, Pasteur Institute of Iran, Tehran. Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Lotfinia
authors.affiliation: Biochemistry Department, Pasteur Institute of Iran, Tehran. Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Saltanatpouri
authors.affiliation: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran. Iran.
authors.forename: Ladan
authors.initials: L
authors.lastname: Teimoori-Toolabi
authors.affiliation: Hybridoma Laboratory, Immunology Department, Pasteur Institute of Iran. Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Sharifzadeh
authors.affiliation: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran. Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Karimipoor
authors.affiliation: Biochemistry Department, Pasteur Institute of Iran, Tehran. Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Kadivar
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003470:Culture Media; D024202:Electrophoretic Mobility Shift Assay; D016259:Genes, myc; D051379:Mice; D008954:Models, Biological; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000201:enzymology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D003470:Culture Media; D009838:Oligodeoxyribonucleotides; D000469:Alkaline Phosphatase
keywords: ESC; Mouse embryonic stem cells; Myc transcription factor; cancer stem cells; decoy ODN; differentiation therapy