Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells.

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Stockhausen MT, Sjolund J, Manetopoulos C, Axelson H

Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells.

Br J Cancer. 2005 Feb 28;92(4):751-9.

PubMed ID

15685243 [ View in PubMed

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Abstract

Neuroblastoma (NB), a sympathetically derived childhood tumour, shows characteristics of neuronal precursor cells, suggesting a halted differentiation process. We have previously shown that the Notch signalling cascade, a key player during normal neurogenesis, also might be involved in NB differentiation. Valproic acid (VPA), a well-tolerated antiepileptic drug, has been shown to induce differentiation and cell death of NB cells, possibly associated with its recently described HDAC inhibiting activity. Stimulation of NB cells with VPA led to increased cell death and phenotypic changes associated with differentiation, that is, neurite extension and upregulation of neuronal markers. VPA treatment also led to an activated Notch signalling cascade as shown by increased levels of intracellular Notch-1 and Hes-1, mimicking the initial phase of induced differentiation. These results reinforce that VPA potentially could be used in differentiation therapy of NB and that the effects in part could be a consequence of interference with the Notch signalling cascade.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Valproic acid	Histone deacetylase 9	Protein	Humans	Yes	Inhibitor	Details