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http://purl.uniprot.org/citations/23557198http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23557198http://www.w3.org/2000/01/rdf-schema#comment"Barasertib, an aurora B inhibitor, terminates cell division, introduces polyploidy, and consequently causes apoptosis. In the present study, we evaluated the effect of the combination of barasertib and cytarabine (ara-C), a key agent for leukemia chemotherapy, on leukemic cells in vitro. Human leukemia HL-60 cells and HL-60/ara-C20 cells, a 20-fold ara-C-resistant variant, were used. The 50% growth inhibitory concentrations of an active metabolite of barasertib, barasertib-hydroxyquinazoline-pyrazol-aniline (Barasertib-HQPA), and ara-C were 51 nM and 300 nM for HL-60 cells and 70 nM and 5300 nM for HL-60/ara-C20 cells, respectively. Barasertib-HQPA induced polyploidy with a subsequent induction of sub-G1 phase apoptosis, indicating the M-phase specific cytotoxicity. Cells treated with the S-phase specific ara-C accumulated in S phase and subsequently died through apoptosis. When HL-60 cells were treated with barasertib-HQPA and ara-C in combination, a greater-than-additive apoptosis was induced. This enhancement was obtained when the cells were treated with barasertib-HQPA prior to ara-C (37.9% sub-G1) or with both concurrently (31.2% sub-G1), but not with ara-C prior to barasertib-HQPA (17.8% sub-G1). The combination effects were similarly obtained in HL-60/ara-C20 cells with 19.7% sub-G1 for barasertib-HQPA→ara-C, 18.4% sub-G1 for both concurrently, and 13.8% sub-G1 for ara-C→barasertib-HQPA, and another leukemic U937 cells with 25.4% sub-G1 for barasertib-HQPA→ara-C, 28.2% sub-G1 for both concurrently, and 16.0% sub-G1 for ara-C→barasertib-HQPA. Barasertib-HQPA inhibited aurora B autophosphorylation and histone H3 phosphorylation in all the cell lines. Barasertib-HQPA did not inhibit DNA synthesis, allowing ara-C incorporation into DNA for its cytotoxicity. Thus, barasertib-HQPA and ara-C provided a greater-than-additive cytotoxicity in leukemic cells in vitro."xsd:string
http://purl.uniprot.org/citations/23557198http://purl.org/dc/terms/identifier"doi:10.1111/cas.12164"xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/author"Yoshida A."xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/author"Ueda T."xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/author"Yamauchi T."xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/author"Negoro E."xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/author"Shigemi H."xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/author"Uzui K."xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/name"Cancer Sci"xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/pages"926-933"xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/title"Aurora B inhibitor barasertib and cytarabine exert a greater-than-additive cytotoxicity in acute myeloid leukemia cells."xsd:string
http://purl.uniprot.org/citations/23557198http://purl.uniprot.org/core/volume"104"xsd:string
http://purl.uniprot.org/citations/23557198http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23557198
http://purl.uniprot.org/citations/23557198http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/23557198
http://purl.uniprot.org/uniprot/#_B2RC06-mappedCitation-23557198http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23557198
http://purl.uniprot.org/uniprot/#_Q96GD4-mappedCitation-23557198http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/23557198
http://purl.uniprot.org/uniprot/Q96GD4http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/23557198
http://purl.uniprot.org/uniprot/B2RC06http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/23557198