Synergistic anti-cancer effects of epigenetic drugs on medulloblastoma cells

Yuan, Jing; Luceño, Núria Llamas; Sander, Bjoern; Golas, Monika M.

doi:10.1007/s13402-017-0319-7

Cited by 20 publications

(16 citation statements)

References 69 publications

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“…Combinations of HDACis with other epigenetic modulators have also been evaluated. SAHA plus the DNA methyltransferase 1 (DNMT) inhibitor 5-aza-2 -deoxycytidine (5-aza-dC) produce a synergistic effect on survival of Daoy and D283 Med MB cells (Yuan et al, 2017).…”

Section: Medulloblastomamentioning

confidence: 99%

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential

Perla

Fratini

Cardoso

et al. 2020

Front. Cell Dev. Biol.

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Brain cancers are the leading cause of cancer-related deaths in children. Biological changes in these tumors likely include epigenetic deregulation during embryonal development of the nervous system. Histone acetylation is one of the most widely investigated epigenetic processes, and histone deacetylase inhibitors (HDACis) are increasingly important candidate treatments in many cancer types. Here, we review advances in our understanding of how HDACis display antitumor effects in experimental models of specific pediatric brain tumor types, i.e., medulloblastoma (MB), ependymoma (EPN), pediatric high-grade gliomas (HGGs), and rhabdoid and atypical teratoid/rhabdoid tumors (ATRTs). We also discuss clinical perspectives for the use of HDACis in the treatment of pediatric brain tumors.

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Section: Medulloblastomamentioning

confidence: 99%

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential

Perla

Fratini

Cardoso

et al. 2020

Front. Cell Dev. Biol.

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“…Using different HDACis, a recent study found a similar effect on neurosphere survival, even in the 8 absence of significant changes in the expression of the stemness marker CD133 (Yuan et al, 2017).…”

Section: Introductionmentioning

confidence: 87%

“…Expression of HDAC2 is higher in patients with MB with poor prognosis (SHH, Group 3 and Group 4), and MYC-amplified MB cell lines show increased mRNA levels of class I HDACs compared to normal cerebellar tissue (Ecker et al, 2015). The antiproliferative effect of HDACi in MB is accompanied by morphological changes, cell cycle arrest, increased expression of glial and neuronal markers, and reduced tumorigenicity (Sonnemann et al, 2006;Spiller et al, 2008;Marino et al, 2011;Nör et al, 2013;Phi et al, 2017;Yuan et al, 2017). We have previously shown that sodium butyrate (NaB), a class I and IIa HDACi, decreases neurosphere formation in MB cultures (Nör et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

HDAC and MAPK/ERK Inhibitors Cooperate to Reduce Viability and Stemness in Medulloblastoma

Jaeger

Ghisleni

Cardoso

et al. 2019

Preprint

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Medulloblastoma (MB), which originates from embryonic neural stem cells (NSCs) or neural precursors in the developing cerebellum, is the most common malignant brain tumor of childhood.Recurrent and metastatic disease is the principal cause of death and may be related to resistance within cancer stem cells (CSCs). Chromatin state is involved in maintaining signaling pathways related to stemness, and inhibition of histone deacetylase enzymes (HDAC) has emerged as a therapeutic tool to target this cell population. Here, we observed changes in the stemness phenotype induced by HDAC inhibition in MB. Analyses of MB tumor samples showed that the stemness markers BMI1 and CD133 are expressed in all molecular subgroups of MB. We then treated human MB cells with the HDAC inhibitor (HDACi) sodium butyrate (NaB). Increased acetylation mediated by NaB reduced cell viability and expression of BMI1 and CD133. Activation of extracellular-regulated kinase (ERK) signaling was also decreased after treatment with NaB.Enrichment analysis of genes associated with CD133 or BMI1 expression showed mitogenactivated protein kinase (MAPK)/ERK signaling and related pathways as the most enriched processes. We went on to use the mitogen-activated protein kinase kinase (MEK) inhibitor U0126 to explore the role of MAPK/ERK pathway. MEK inhibition reduced expression of the stemness markers, hindered MB neurosphere formation, and its antiproliferative effect was enhanced by combination with NaB. These results suggest that combining HDAC and MAPK/ERK inhibitors may be more effective in reducing MB proliferation than single-drug treatments, through modulation of the stemness phenotype of MB cells. 5 Keywords: Histone deacetylase Extracellular-regulated kinase Stemness Medulloblastoma Brain tumor 6

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“…PN has been reported to act as an epigenetic drug inhibiting both HDAC1 [20] and DNMT1 [67]. In combination with 5-aza-2 -deoxycytidine, an inhibitor of DNMT1, PN synergistically reduced growth and induced apoptosis of medulloblastoma-derived cells [129].…”

Section: Parthenolide Combined With Alkylating Agentsmentioning

confidence: 99%

Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies

Sztiller-Sikorska¹,

Czyż²

2020

Pharmaceuticals

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Primary and acquired resistance of cancer to therapy is often associated with activation of nuclear factor kappa B (NF-κB). Parthenolide (PN) has been shown to inhibit NF-κB signaling and other pro-survival signaling pathways, induce apoptosis and reduce a subpopulation of cancer stem-like cells in several cancers. Multimodal therapies that include PN or its derivatives seem to be promising approaches enhancing sensitivity of cancer cells to therapy and diminishing development of resistance. A number of studies have demonstrated that several drugs with various targets and mechanisms of action can cooperate with PN to eliminate cancer cells or inhibit their proliferation. This review summarizes the current state of knowledge on PN activity and its potential utility as complementary therapy against different cancers.

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Synergistic anti-cancer effects of epigenetic drugs on medulloblastoma cells

Abstract: Our current results suggest that the application of HDACi in combination with drugs that target DNMT may represent a promising option for the treatment of medulloblastoma.

Cited by 20 publications

References 69 publications

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential

HDAC and MAPK/ERK Inhibitors Cooperate to Reduce Viability and Stemness in Medulloblastoma

Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies

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