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The Histone Deacetylase Inhibitor Sodium Butyrate Promotes Cell Death and Differentiation and Reduces Neurosphere Formation in Human Medulloblastoma Cells

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Abstract

Increasing evidence suggests that alterations in epigenetic mechanisms regulating chromatin state play a role in the pathogenesis of medulloblastoma (MB), the most common malignant brain tumor of childhood. Histone deacetylase (HDAC) inhibitors, which increase chromatin relaxation, have been shown to display anticancer activities. Here we show that the HDAC inhibitor sodium butyrate (NaB) markedly increases cell death and reduces colony formation in human MB cell lines. In addition, NaB increased the mRNA expression of Gria2, a neuronal differentiation marker, in D283 and DAOY cells and reduced the number of neurospheres in D283 cell cultures. Finally, NaB reduced the viability of D283 cells when combined with etoposide. These data show that NaB displays pronounced inhibitory effects on the survival of human MB cells and suggest that NaB might potentiate the effects of etoposide. In addition, our study suggests that HDAC inhibition might promote the neuronal differentiation of MB cells and provides the first evidence that an HDAC inhibitor might suppress the expansion or survival of MB cancer stem cells.

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Acknowledgments

This research was supported by the National Council for Scientific and Technological Development (CNPq; grant numbers 303703/2009-1 and 484185/2012-8 to R.R); the Rafael Koff Acordi Research Fund, Children’s Cancer Institute (ICI-RS); the National Institute for Translational Medicine (INCT-TM); and the South American Office for Anticancer Drug Development. C.N. and F.A.S are supported by CNPq graduate fellowships.

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Authors and Affiliations

  1. Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Carolina Nör, Felipe A. Sassi, Caroline Brunetto de Farias, Gilberto Schwartsmann, Ana Lucia Abujamra, Algemir Lunardi Brunetto & Rafael Roesler

  2. Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), 90050-170, Porto Alegre, RS, Brazil

    Carolina Nör, Felipe A. Sassi & Rafael Roesler

  3. National Institute for Translational Medicine, Porto Alegre, RS, Brazil

    Carolina Nör, Felipe A. Sassi, Caroline Brunetto de Farias, Gilberto Schwartsmann, Ana Lucia Abujamra, Algemir Lunardi Brunetto & Rafael Roesler

  4. Children’s Cancer Institute (ICI-RS) and Pediatric Oncology Unit, University Hospital (HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Caroline Brunetto de Farias, Ana Lucia Abujamra & Algemir Lunardi Brunetto

  5. School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Gilberto Schwartsmann & Algemir Lunardi Brunetto

  6. Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Guido Lenz

  7. Center for Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Guido Lenz

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  1. Carolina Nör
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  2. Felipe A. Sassi
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Correspondence to Rafael Roesler.

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Nör, C., Sassi, F.A., de Farias, C.B. et al. The Histone Deacetylase Inhibitor Sodium Butyrate Promotes Cell Death and Differentiation and Reduces Neurosphere Formation in Human Medulloblastoma Cells. Mol Neurobiol 48, 533–543 (2013). https://doi.org/10.1007/s12035-013-8441-7

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