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Aurora kinases as targets in drug-resistant neuroblastoma cells

Michaelis, Martin, Selt, Florian, Rothweiler, Florian, Löschmann, Nadine, Nüsse, Benedikt, Dirks, Wilhelm G, Zehner, Richard, Cinatl, Jindrich (2014) Aurora kinases as targets in drug-resistant neuroblastoma cells. PloS one, 9 (9). ISSN 1932-6203. (doi:10.1371/journal.pone.0108758) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1371/journal.pone.0108758

Abstract

Aurora kinase inhibitors displayed activity in pre-clinical neuroblastoma models. Here, we studied the effects of the pan-aurora kinase inhibitor tozasertib (VX680, MK-0457) and the aurora kinase inhibitor alisertib (MLN8237) that shows some specificity for aurora kinase A over aurora kinase B in a panel of neuroblastoma cell lines with acquired drug resistance. Both compounds displayed anti-neuroblastoma activity in the nanomolar range. The anti-neuroblastoma mechanism included inhibition of aurora kinase signalling as indicated by decreased phosphorylation of the aurora kinase substrate histone H3, cell cycle inhibition in G2/M phase, and induction of apoptosis. The activity of alisertib but not of tozasertib was affected by ABCB1 expression. Aurora kinase inhibitors induced a p53 response and their activity was enhanced in combination with the MDM2 inhibitor and p53 activator nutlin-3 in p53 wild-type cells. In conclusion, aurora kinases are potential drug targets in therapy-refractory neuroblastoma, in particular for the vast majority of p53 wild-type cases.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0108758
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 02 Oct 2014 19:29 UTC
Last Modified: 29 May 2019 13:08 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/43173 (The current URI for this page, for reference purposes)
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