TY  - JOUR
A1  - Michaelis, Martin
A1  - Selt, Florian
A1  - Rothweiler, Florian
A1  - Löschmann, Nadine
A1  - Nüsse, Benedikt
A1  - Dirks, Wilhelm G.
A1  - Zehner, Richard
A1  - Cinatl, Jindrich
T1  - Aurora kinases as targets in drug-resistant neuroblastoma cells
T2  - PLoS One
N2  - 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.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/35101
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-351010
SN  - 1932-6203
N1  - Copyright: © 2014 Michaelis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 9
IS  - (9):e108758
PB  - PLoS
CY  - Lawrence, Kan.
ER  -