Abstract
Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: The optimized Myc decoy ODNs approach might be considered as a promising alternative strategy for differentiation therapy investigations.
Keywords: Mouse embryonic stem cells, decoy ODN, Myc transcription factor, cancer stem cells, differentiation therapy, ESC.
Anti-Cancer Agents in Medicinal Chemistry
Title:Myc Decoy Oligodeoxynucleotide Inhibits Growth and Modulates Differentiation of Mouse Embryonic Stem Cells as a Model of Cancer Stem Cells
Volume: 17 Issue: 13
Author(s): Behrooz Johari, Mina Ebrahimi-Rad, Faezeh Maghsood, Majid Lotfinia, Zohreh Saltanatpouri, Ladan Teimoori-Toolabi, Zahra Sharifzadeh, Morteza Karimipoor and Mehdi Kadivar*
Affiliation:
- Biochemistry Department, Pasteur Institute of Iran, Tehran,Iran
Keywords: Mouse embryonic stem cells, decoy ODN, Myc transcription factor, cancer stem cells, differentiation therapy, ESC.
Abstract: Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: The optimized Myc decoy ODNs approach might be considered as a promising alternative strategy for differentiation therapy investigations.
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Johari Behrooz , Ebrahimi-Rad Mina , Maghsood Faezeh, Lotfinia Majid, Saltanatpouri Zohreh, Teimoori-Toolabi Ladan, Sharifzadeh Zahra, Karimipoor Morteza and Kadivar Mehdi*, Myc Decoy Oligodeoxynucleotide Inhibits Growth and Modulates Differentiation of Mouse Embryonic Stem Cells as a Model of Cancer Stem Cells, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (13) . https://dx.doi.org/10.2174/1871521409666170412142507
DOI https://dx.doi.org/10.2174/1871521409666170412142507 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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