A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance in chronic myeloid leukemia cells

  • Authors:
    • Zi-Jie Long
    • Le-Xun Wang
    • Fei-Meng Zheng
    • Jia-Jie Chen
    • Yu Luo
    • Xi-Xiang Tu
    • Dong-Jun Lin
    • Gui Lu
    • Quentin Liu
  • View Affiliations

  • Published online on: April 9, 2015     https://doi.org/10.3892/ijo.2015.2960
  • Pages: 2488-2496
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Abstract

Drug resistance still represents a major obstacle to successful chronic myeloid leukemia (CML) treatment and novel compounds or strategies to override this challenging problem are urgently required. Here, we evaluated a novel compound AKI603 against oncogenic Aurora kinase A (Aur-A) in imatinib-resistant CML cells. We found that Aur-A was highly activated in imatinib-resistant KBM5-T315I cells. AKI603 significantly inhibited the phosphorylation of Aur-A kinase at Thr288, while had little inhibitory effect on BCR-ABL kinase in both KBM5 and KBM5-T315I cells. AKI603 inhibited cell viability, and induced cell cycle arrest with polyploidy accumulation in KBM5 and KBM5-T315I cells. Moreover, inhibition of Aur-A kinase by AKI603 suppressed colony formation capacity without promoting obvious apoptosis. Importantly, AKI603 promoted cell differentiation in both CML cell types. Thus, our study suggested the potential clinical use of small molecule Aurora kinase inhibitor AKI603 to overcome imatinib resistance in CML treatment.
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June-2015
Volume 46 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Long Z, Wang L, Zheng F, Chen J, Luo Y, Tu X, Lin D, Lu G and Liu Q: A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance in chronic myeloid leukemia cells. Int J Oncol 46: 2488-2496, 2015
APA
Long, Z., Wang, L., Zheng, F., Chen, J., Luo, Y., Tu, X. ... Liu, Q. (2015). A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance in chronic myeloid leukemia cells. International Journal of Oncology, 46, 2488-2496. https://doi.org/10.3892/ijo.2015.2960
MLA
Long, Z., Wang, L., Zheng, F., Chen, J., Luo, Y., Tu, X., Lin, D., Lu, G., Liu, Q."A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance in chronic myeloid leukemia cells". International Journal of Oncology 46.6 (2015): 2488-2496.
Chicago
Long, Z., Wang, L., Zheng, F., Chen, J., Luo, Y., Tu, X., Lin, D., Lu, G., Liu, Q."A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance in chronic myeloid leukemia cells". International Journal of Oncology 46, no. 6 (2015): 2488-2496. https://doi.org/10.3892/ijo.2015.2960