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MYCN concurrence with SAHA-induced cell death in human neuroblastoma cells

Cellular Oncology volume 38, pages 341–352 (2015)Cite this article

Abstract

Background

In the past, the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) has been shown to induce apoptosis in several human tumor types, including neuroblastomas. Amplification and over-expression of the MYCN oncogene is a diagnostic hallmark and a poor prognostic indicator in high-risk neuroblastomas. Here, we studied the relationship between MYCN amplification and over-expression and the anti-tumor effect of SAHA to assess whether this drug may serve as a treatment option for high-risk neuroblastomas.

Methods

Different human neuroblastoma cell lines, over-expressing or not over-expressing MYCN, were used in this study. Targeted knockdown and exogenous over-expression of MYCN were employed to examine correlations between MYCN expression levels and SAHA responses. After various time periods and concentration exposures to the drug, cell viability was measured by MTS assay, and variations in MYCN mRNA and protein levels were assessed by qPCR and Western blotting, respectively.

Results

We found that SAHA decreased cell viability in all cell lines tested through apoptosis induction, and that SAHA had a stronger effect on cell lines carrying an amplified MYCN gene. A decrease in MYCN mRNA and protein levels was observed in the SAHA treated cell lines. Subsequent silencing and exogenous over-expression of MYCN changed the proliferation rate of the cells, but did not have any significant impact on the effect of SAHA on the viability of the cells. We also found that SAHA blocked the expression of MYCN and, by doing so, reduced the effects mediated by this protein.

Conclusions

Our results suggest that SAHA may be used as a single-drug treatment option for neuroblastomas with an amplified MYCN gene, and as an adjuvant treatment option for all neuroblastomas.

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Acknowledgments

We are grateful to Megumi Iisasa for correcting the English language. This work was supported by Dirección General de Investigación Científica y Técnica, BFU2009-09933 to A.T. and BFU2012-38867 to S.C.K. and A.T., as well as by Red Temática de Investigación Cooperativa en Cáncer, RD12/0036/0049 to A.T. and S.C.K. and RD12/0036/0029 to S.A. Constanza Cortés was recipient of a fellowship from Universitat de Barcelona.

Competing interests

The authors declare that they have no competing interests.

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Affiliations

  1. Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Universitat de Barcelona, 08028, Barcelona, Catalunya, Spain

    Constanza Cortés & Albert Tauler

  2. Laboratory of Cancer Metabolism, IDIBELL, Hospital Duran i Reynals, L’Hospitalet de Llobregat, Catalunya, 08907, Spain

    Constanza Cortés, Sara C. Kozma & Albert Tauler

  3. Unitat de Bioquímica, Dep. Ciències Fisiològiques II, Facultat de Medicina, Campus Universitari de Bellvitge - IDIBELL, Universitat de Barcelona, L’Hospitalet de Llobregat, Catalunya, 08907, Spain

    Santiago Ambrosio

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  1. Constanza Cortés
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  2. Sara C. Kozma
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  3. Albert Tauler
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  4. Santiago Ambrosio
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Correspondence to Santiago Ambrosio.

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Cortés, C., Kozma, S.C., Tauler, A. et al. MYCN concurrence with SAHA-induced cell death in human neuroblastoma cells. Cell Oncol. 38, 341–352 (2015). https://doi.org/10.1007/s13402-015-0233-9

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Keywords

  • Neuroblastoma
  • MYCN
  • SAHA