Aurora Kinases as Targets in Drug-Resistant Neuroblastoma Cells
Publication Date
September 30, 2014
Journal
PLOS ONE
Authors
Martin Michaelis, Florian Selt, Florian Rothweiler, Nadine Löschmann, et al
Volume
9
Issue
9
Pages
e108758
DOI
https://dx.plos.org/10.1371/journal.pone.0108758
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0108758
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25268132
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182628
Europe PMC
http://europepmc.org/abstract/MED/25268132
Web of Science
000343671700158
Scopus
84907560588
Mendeley
http://www.mendeley.com/research/aurora-kinases-targets-drugresistant-neuroblastoma-cells
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1698967"], "description"=>"<p>Expression levels are presented as fold change relative to non-treated controls. * P<0.05 relative to non-treated control.</p>", "links"=>[], "tags"=>["p 53 response", "MDM 2 inhibitor", "aurora kinase inhibitor alisertib", "neuroblastoma cell lines", "vx", "mk", "aurora kinase B", "ABCB 1 expression", "aurora kinase", "mln", "Aurora kinase inhibitors"], "article_id"=>1188848, "categories"=>["Biological Sciences"], "users"=>["Martin Michaelis", "Florian Selt", "Florian Rothweiler", "Nadine Löschmann", "Benedikt Nüsse", "Wilhelm G. Dirks", "Richard Zehner", "Jindrich Cinatl Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0108758.g002", "stats"=>{"downloads"=>4, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tozasertib_1_181_M_induced_expression_of_p53_target_genes_as_indicated_by_qPCR_/1188848", "title"=>"Tozasertib (1 µM)-induced expression of p53 target genes as indicated by qPCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-30 04:01:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1698984", "https://ndownloader.figshare.com/files/1698985", "https://ndownloader.figshare.com/files/1698986", "https://ndownloader.figshare.com/files/1698988", "https://ndownloader.figshare.com/files/1698990"], "description"=>"<div><p>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.</p></div>", "links"=>[], "tags"=>["p 53 response", "MDM 2 inhibitor", "aurora kinase inhibitor alisertib", "neuroblastoma cell lines", "vx", "mk", "aurora kinase B", "ABCB 1 expression", "aurora kinase", "mln", "Aurora kinase inhibitors"], "article_id"=>1188865, "categories"=>["Biological Sciences"], "users"=>["Martin Michaelis", "Florian Selt", "Florian Rothweiler", "Nadine Löschmann", "Benedikt Nüsse", "Wilhelm G. Dirks", "Richard Zehner", "Jindrich Cinatl Jr"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0108758.s001", "https://dx.doi.org/10.1371/journal.pone.0108758.s002", "https://dx.doi.org/10.1371/journal.pone.0108758.s003", "https://dx.doi.org/10.1371/journal.pone.0108758.s004", "https://dx.doi.org/10.1371/journal.pone.0108758.s005"], "stats"=>{"downloads"=>9, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Aurora_Kinases_as_Targets_in_Drug_Resistant_Neuroblastoma_Cells_/1188865", "title"=>"Aurora Kinases as Targets in Drug-Resistant Neuroblastoma Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-09-30 04:01:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1698969"], "description"=>"<p>A) tozasertib-induced p53 and p21 expression as indicated by Western blot after 24 h of incubation; B) tozasertib- and alisertib-induced expression of p53 target genes in UKF-NB-3 cells in which p53 was depleted using a lentiviral vector encoding shRNA directed against p53 (UKF-NB-3<sup>p53shRNA</sup>) or in UKF-NB-3 cells transduced with a control vector encoding non-targeting scramble shRNA (UKF-NB-3<sup>scr</sup>) as indicated by qPCR after 24 h. Expression levels are presented as fold change relative to non-treated controls. * P<0.05 relative to non-treated control; C) tozasertib and alisertib concentrations that reduce UKF-NB-3, UKF-NB-3<sup>scr</sup>, and UKF-NB-3<sup>p53shRNA</sup> viability by 50% (IC<sub>50</sub>). * P<0.05 relative to UKF-NB-3 cells.</p>", "links"=>[], "tags"=>["p 53 response", "MDM 2 inhibitor", "aurora kinase inhibitor alisertib", "neuroblastoma cell lines", "vx", "mk", "aurora kinase B", "ABCB 1 expression", "aurora kinase", "mln", "Aurora kinase inhibitors"], "article_id"=>1188851, "categories"=>["Biological Sciences"], "users"=>["Martin Michaelis", "Florian Selt", "Florian Rothweiler", "Nadine Löschmann", "Benedikt Nüsse", "Wilhelm G. Dirks", "Richard Zehner", "Jindrich Cinatl Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0108758.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Role_of_p53_signalling_in_response_to_aurora_kinase_inhibition_/1188851", "title"=>"Role of p53 signalling in response to aurora kinase inhibition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-30 04:01:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1698973"], "description"=>"<p>Neuroblastoma cells were treated for five days with tozasertib, nutlin-3, or their combination. Cell viability was determined by MTT assay. The drug concentrations were: UKF-NB-3, tozasertib 6 nM, Nutlin-3 0.625 µM; IMR-32, tozasertib 6 nM, Nutlin-3 1.25 µM; UKF-NB-3<sup>r</sup>CDDP<sup>1000</sup>, tozasertib 6 nM, Nutlin-3 1.25 µM; UKF-NB-3<sup>r</sup>DOX<sup>20</sup>, tozasertib 156 nM, Nutlin-3 2.5 µM; UKF-NB-3<sup>r</sup>Nutlin<sup>10µM</sup>, tozasertib 156 nM, Nutlin-3 5 µM; UKF-NB-3<sup>r</sup>VCR<sup>10</sup>, tozasertib 156 nM, Nutlin-3 5 µM. * P<0.05 relative to either single treatment.</p>", "links"=>[], "tags"=>["p 53 response", "MDM 2 inhibitor", "aurora kinase inhibitor alisertib", "neuroblastoma cell lines", "vx", "mk", "aurora kinase B", "ABCB 1 expression", "aurora kinase", "mln", "Aurora kinase inhibitors"], "article_id"=>1188855, "categories"=>["Biological Sciences"], "users"=>["Martin Michaelis", "Florian Selt", "Florian Rothweiler", "Nadine Löschmann", "Benedikt Nüsse", "Wilhelm G. Dirks", "Richard Zehner", "Jindrich Cinatl Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0108758.g004", "stats"=>{"downloads"=>4, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_tozasertib_on_the_viability_of_neuroblastoma_cells_in_combination_with_the_MDM2_inhibitor_nutlin_3_/1188855", "title"=>"Effects of tozasertib on the viability of neuroblastoma cells in combination with the MDM2 inhibitor nutlin-3.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-30 04:01:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1698982"], "description"=>"<p>* P<0.05 relative to UKF-NB-3<sup>scr</sup>.</p>", "links"=>[], "tags"=>["p 53 response", "MDM 2 inhibitor", "aurora kinase inhibitor alisertib", "neuroblastoma cell lines", "vx", "mk", "aurora kinase B", "ABCB 1 expression", "aurora kinase", "mln", "Aurora kinase inhibitors"], "article_id"=>1188863, "categories"=>["Biological Sciences"], "users"=>["Martin Michaelis", "Florian Selt", "Florian Rothweiler", "Nadine Löschmann", "Benedikt Nüsse", "Wilhelm G. Dirks", "Richard Zehner", "Jindrich Cinatl Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0108758.g006", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tozasertib_induced_apoptosis_in_UKF_NB_3_cells_transduced_with_a_lentiviral_vector_encoding_shRNA_directed_against_p53_UKF_NB_3_p53shRNA_and_UKF_NB_3_transduced_with_a_control_vector_expressing_non_targeting_scrambled_shRNA_UKF_NB_3_scr_as_indicated_by_B/1188863", "title"=>"Tozasertib-induced apoptosis in UKF-NB-3 cells transduced with a lentiviral vector encoding shRNA directed against p53 (UKF-NB-3<sup>p53shRNA</sup>) and UKF-NB-3 transduced with a control vector expressing non-targeting scrambled shRNA (UKF-NB-3<sup>scr</sup>) as indicated by BAX activation, caspase 3/7 activation, and determination of sub-G1 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-30 04:01:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1698979"], "description"=>"<p>A) Numbers of cells expressing phosphorylated histone H3 were determined flow cytometry; * P<0.05 relative to untreated control; B) Representative histograms indicating cell cycle distribution in neuroblastoma cells after tozasertib treatment, arrows indicate additional peaks with high DNA content, possibly indicating endoreduplication; C) Numbers of cells with activated BAX expressed as fold change relative to control as determined by flow cytometry using an antibody specific for activated BAX after 24 h of tozasertib treatment. * P<0.05 relative to untreated control.</p>", "links"=>[], "tags"=>["p 53 response", "MDM 2 inhibitor", "aurora kinase inhibitor alisertib", "neuroblastoma cell lines", "vx", "mk", "aurora kinase B", "ABCB 1 expression", "aurora kinase", "mln", "Aurora kinase inhibitors"], "article_id"=>1188860, "categories"=>["Biological Sciences"], "users"=>["Martin Michaelis", "Florian Selt", "Florian Rothweiler", "Nadine Löschmann", "Benedikt Nüsse", "Wilhelm G. Dirks", "Richard Zehner", "Jindrich Cinatl Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0108758.g005", "stats"=>{"downloads"=>4, "page_views"=>62, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_tozasertib_on_histone_H3_phosphorylation_indicating_aurora_kinase_A_and_B_activity_cell_cycle_distribution_and_apoptosis_indicated_by_BAX_activation_in_neuroblastoma_cells_/1188860", "title"=>"Effects of tozasertib on histone H3 phosphorylation (indicating aurora kinase A and B activity), cell cycle distribution, and apoptosis (indicated by BAX activation) in neuroblastoma cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-30 04:01:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1698966"], "description"=>"<p>A) IC<sub>50</sub> values determined after 120 h of incubation by MTT assay; B) tozasertib IC<sub>50</sub> values in the presence of the ABCB1 inhibitor zosuquidar (5 µM); C) Average IC<sub>50</sub> values in high and low ABCB1-expressing cells, * P<0.05 compared to low ABCB1-expressing cells; D) IC<sub>50</sub> values in UKF-NB-3 cells, UKF-NB-3 cells transduced with a lentiviral vector encoding for ABCB1 (UKF-NB-3<sup>ABCB1</sup>), and UKF-NB-3 cells transduced with a control vector (UKF-NB-3<sup>control</sup>), * P<0.05 compared to UKF-NB-3.</p>", "links"=>[], "tags"=>["p 53 response", "MDM 2 inhibitor", "aurora kinase inhibitor alisertib", "neuroblastoma cell lines", "vx", "mk", "aurora kinase B", "ABCB 1 expression", "aurora kinase", "mln", "Aurora kinase inhibitors"], "article_id"=>1188847, "categories"=>["Biological Sciences"], "users"=>["Martin Michaelis", "Florian Selt", "Florian Rothweiler", "Nadine Löschmann", "Benedikt Nüsse", "Wilhelm G. Dirks", "Richard Zehner", "Jindrich Cinatl Jr"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0108758.g001", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_tozasertib_and_alisertib_on_neuroblastoma_cell_viability_/1188847", "title"=>"Effects of tozasertib and alisertib on neuroblastoma cell viability.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-30 04:01:46"}

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Medicine and health sciences", "average_usage"=>[285]}, {"subject_area"=>"/Medicine and health sciences/Oncology", "average_usage"=>[266]}]}
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