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International Journal of Molecular Medicine
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Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin

  • Authors:
    • Stephanie S. Wang
    • Ruth Hsiao
    • Mariko M. Limpar
    • Sarah Lomahan
    • Tuan-Anh Tran
    • Nolan J. Maloney
    • Naohiko Ikegaki
    • Xao X. Tang
  • View Affiliations / Copyright

    Affiliations: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 35-42
    |
    Published online on: November 1, 2013
       https://doi.org/10.3892/ijmm.2013.1545
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Abstract

In the present study, we investigated the anticancer effects of the mitochondrial inhibitors, metaiodobenzylguanidine (MIBG), metformin and phenformin. 131I-MIBG has been used for scintigraphic detection and the targeted radiotherapy of neuroblastoma (NB), a pediatric malignancy. Non-radiolabeled MIBG has been reported to be cytotoxic to NB cells in vitro and in vivo. However, the mechanisms behind its growth suppressive effects have not yet been fully elucidated. Metformin and phenformin are diabetes medications that are being considered in anticancer therapeutics. We investigated the anticancer mechanisms of action of MIBG and metformin in NB. Our data revealed that both drugs suppressed NB cell growth and that the combination drug treatment was more potent. MIBG reduced MYCN and MYC expression in MYCN-amplified and non-MYCN-amplified NB cells in a dose- and time-dependent manner. Metformin was less effective than MIBG in destabilizing MYC/MYCN. The treatment of NB cells with metformin or MIBG resulted in an increased expression of genes encoding biomarkers for favorable outcome in NB [(ephrin (EFN)B2, EFNB3, EPH receptor B6 (EPHB6), neurotrophic tyrosine kinase, receptor, type 1 (NTRK1), CD44 and Myc-interacting zinc finger protein (MIZ-1)] and tumor suppressor genes [(early growth response 1 (EGR1), EPH receptor A2 (EPHA2), growth arrest and DNA-damage-inducible, beta (GADD45B), neuregulin 1 (NRG1), TP53 apoptosis effector (PERP) and sel-1 suppressor of lin-12-like (C. elegans) (SEL1L)]. Accordingly, metformin and MIBG augmented histone H3 acetylation in these cells. Phenformin also exhibited histone modification and was more effective than metformin in destabilizing MYC/MYCN in NB cells. Our data suggest that the destabilization of MYC/MYCN by MIBG, metformin and phenformin and their effects on histone modification are important mechanisms underlying their anticancer effects.
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Copy and paste a formatted citation
Spandidos Publications style
Wang SS, Hsiao R, Limpar MM, Lomahan S, Tran T, Maloney NJ, Ikegaki N and Tang XX: Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin. Int J Mol Med 33: 35-42, 2014.
APA
Wang, S.S., Hsiao, R., Limpar, M.M., Lomahan, S., Tran, T., Maloney, N.J. ... Tang, X.X. (2014). Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin. International Journal of Molecular Medicine, 33, 35-42. https://doi.org/10.3892/ijmm.2013.1545
MLA
Wang, S. S., Hsiao, R., Limpar, M. M., Lomahan, S., Tran, T., Maloney, N. J., Ikegaki, N., Tang, X. X."Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin". International Journal of Molecular Medicine 33.1 (2014): 35-42.
Chicago
Wang, S. S., Hsiao, R., Limpar, M. M., Lomahan, S., Tran, T., Maloney, N. J., Ikegaki, N., Tang, X. X."Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin". International Journal of Molecular Medicine 33, no. 1 (2014): 35-42. https://doi.org/10.3892/ijmm.2013.1545
Copy and paste a formatted citation
x
Spandidos Publications style
Wang SS, Hsiao R, Limpar MM, Lomahan S, Tran T, Maloney NJ, Ikegaki N and Tang XX: Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin. Int J Mol Med 33: 35-42, 2014.
APA
Wang, S.S., Hsiao, R., Limpar, M.M., Lomahan, S., Tran, T., Maloney, N.J. ... Tang, X.X. (2014). Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin. International Journal of Molecular Medicine, 33, 35-42. https://doi.org/10.3892/ijmm.2013.1545
MLA
Wang, S. S., Hsiao, R., Limpar, M. M., Lomahan, S., Tran, T., Maloney, N. J., Ikegaki, N., Tang, X. X."Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin". International Journal of Molecular Medicine 33.1 (2014): 35-42.
Chicago
Wang, S. S., Hsiao, R., Limpar, M. M., Lomahan, S., Tran, T., Maloney, N. J., Ikegaki, N., Tang, X. X."Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin". International Journal of Molecular Medicine 33, no. 1 (2014): 35-42. https://doi.org/10.3892/ijmm.2013.1545
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