title: The histone deacetylase inhibitor sodium butyrate promotes cell death and differentiation and reduces neurosphere formation in human medulloblastoma cells.
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.
authors.affiliation: Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Nör
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Sassi
authors.forename: Caroline Brunetto
authors.initials: CB
authors.lastname: de Farias
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Abujamra
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.forename: Algemir Lunardi
authors.initials: AL
authors.lastname: Brunetto
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D020148:Butyric Acid / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D020148:Butyric Acid; D005047:Etoposide