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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2034-2040. Prepublished online as a Blood First Edition Paper on May 10, 2007; DOI 10.1182/blood-2007-02-073700. This Article Full Text (PDF) All Versions of this Article: blood-2007-02-073700v1 110/6/2034    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yang, J. Articles by Yokoyama, A. Search for Related Content PubMed PubMed Citation Articles by Yang, J. Articles by Yokoyama, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2007 Accepted April 28, 2007 AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo Jing Yang, Takayuki Ikezoe*, Chie Nishioka, Taizo Tasaka, Ayuko Taniguchi, Yoshio Kuwayama, Naoki Komatsu, Kentaro Bandobashi, Kazuto Togitani, H.Phillip Koeffler, Hirokuni Taguchi, and Akihito Yokoyama Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Japan Division of Hematology, Department of Medicine, Kawasaki Medical School, Kurashiki, Japan Department of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA, United States * Corresponding author; email: ikezoet{at}kochi-u.ac.jp. Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. We have recently shown that hematopoietic malignant cells including those from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) aberrantly expressed Aurora A and B kinases, and ZM447439, a potent inhibitor of Aurora kinases, effectively induced growth arrest and apoptosis of a variety of leukemia cells. The present study explored the effect of AZD1152, a highly selective inhibitor of Aurora B kinase, on various types of human leukemia cells. AZD1152 inhibited the proliferation of AML lines (HL-60, NB4, MOLM13), ALL line (PALL-2), biphenotypic leukemia (MV4-11), acute eosinophilic leukemia (EOL-1), and the blast crisis of chronic myeloid leukemia K562 cells with an IC50 ranging from 3 to 40 nM, as measured by thymidine uptake on day 2 of culture. These cells had 4N/8N DNA content followed by apoptosis, as measured by cell cycle analysis and annexin V staining, respectively. Of note, AZD1152 synergistically enhanced the anti-proliferative activity of vincristine, a tubulin depolymerazing agent, or daunorubicin, a topoisomerase II inhibitor, against the MOLM13 and PALL-2 cells in vitro. Furthermore, AZD1152 potentiated the action of vincristine or daunorubicin in a MOLM13 murine xenograph model. Taken together, AZD1152 is a promising new agent for treatment of individuals with leukemia. The combined administration of AZD1152 and conventional chemotherapeutic agent to patients with leukemia warrants further investigation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. S. Boss, J. H. Beijnen, and J. H.M. Schellens Clinical Experience with Aurora Kinase Inhibitors: A Review Oncologist, August 1, 2009; 14(8): 780 - 793. [Abstract] [Full Text] [PDF] A. G. Renner, C. Dos Santos, C. Recher, C. Bailly, L. Creancier, A. Kruczynski, B. Payrastre, and S. Manenti Polo-like kinase 1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells Blood, July 16, 2009; 114(3): 659 - 662. [Abstract] [Full Text] [PDF] A. Oke, D. Pearce, R. W. Wilkinson, C. Crafter, R. Odedra, J. Cavenagh, J. Fitzgibbon, A. T. Lister, S. Joel, and D. Bonnet AZD1152 Rapidly and Negatively Affects the Growth and Survival of Human Acute Myeloid Leukemia Cells In vitro and In vivo Cancer Res., May 15, 2009; 69(10): 4150 - 4158. [Abstract] [Full Text] [PDF] E. C. VanderPorten, P. Taverna, J. N. Hogan, M. D. Ballinger, W. M. Flanagan, and R. V. Fucini The Aurora kinase inhibitor SNS-314 shows broad therapeutic potential with chemotherapeutics and synergy with microtubule-targeted agents in a colon carcinoma model Mol. Cancer Ther., April 1, 2009; 8(4): 930 - 939. [Abstract] [Full Text] [PDF] J. S. Nair, E. de Stanchina, and G. K. Schwartz The Topoisomerase I Poison CPT-11 Enhances the Effect of the Aurora B Kinase Inhibitor AZD1152 both In vitro and In vivo Clin. Cancer Res., March 15, 2009; 15(6): 2022 - 2030. [Abstract] [Full Text] [PDF] D. O. Cowley, J. A. Rivera-Perez, M. Schliekelman, Y. J. He, T. G. Oliver, L. Lu, R. O'Quinn, E. D. Salmon, T. Magnuson, and T. Van Dyke Aurora-A Kinase Is Essential for Bipolar Spindle Formation and Early Development Mol. Cell. Biol., February 15, 2009; 29(4): 1059 - 1071. [Abstract] [Full Text] [PDF] T.-L. Cha, M.-J. Chuang, S.-T. Wu, G.-H. Sun, S.-Y. Chang, D.-S. Yu, S.-M. Huang, S. K.-H. Huan, T.-C. Cheng, T.-T. Chen, et al. Dual Degradation of Aurora A and B Kinases by the Histone Deacetylase Inhibitor LBH589 Induces G2-M Arrest and Apoptosis of Renal Cancer Cells Clin. Cancer Res., February 1, 2009; 15(3): 840 - 850. [Abstract] [Full Text] [PDF] T. Ochi, H. Fujiwara, K. Suemori, T. Azuma, Y. Yakushijin, T. Hato, K. Kuzushima, and M. Yasukawa Aurora-A kinase: a novel target of cellular immunotherapy for leukemia Blood, January 1, 2009; 113(1): 66 - 74. [Abstract] [Full Text] [PDF] X.-B. Wan, Z.-J. Long, M. Yan, J. Xu, L.-P. Xia, L. Liu, Y. Zhao, X.-F. Huang, X.-R. Wang, X.-F. Zhu, et al. Inhibition of Aurora-A suppresses epithelial-mesenchymal transition and invasion by downregulating MAPK in nasopharyngeal carcinoma cells Carcinogenesis, October 1, 2008; 29(10): 1930 - 1937. [Abstract] [Full Text] [PDF] W. Fiskus, Y. Wang, R. Joshi, R. Rao, Y. Yang, J. Chen, R. Kolhe, R. Balusu, K. Eaton, P. Lee, et al. Cotreatment with Vorinostat Enhances Activity of MK-0457 (VX-680) against Acute and Chronic Myelogenous Leukemia Cells Clin. Cancer Res., October 1, 2008; 14(19): 6106 - 6115. [Abstract] [Full Text] [PDF] K. Kojima, M. Konopleva, T. Tsao, H. Nakakuma, and M. Andreeff Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia Blood, October 1, 2008; 112(7): 2886 - 2895. [Abstract] [Full Text] [PDF]

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