Orally Active Aurora A/B Kinase Inhibitor, AM-005, Suppresses the Growth of Human Colon Carcinoma Cells

Authors

  • Ming Zheng,

    1. Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, China
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    • These two authors contributed equally to this work.
  • Youguang Zheng,

    1. School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu, China
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    • These two authors contributed equally to this work.
  • Li Xie,

    1. Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, China
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  • Weiwei Chang,

    1. Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, China
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  • Ning Gu,

    1. Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, China
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  • Min Ji

    Corresponding author
    • School of Chemistry and Chemical Engineering, Southeast University, Nanjing, Jiangsu, China
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  • Conflict of interest: The authors declare that they have no conflict of interest.

Correspondence to: Min Ji, School of Chemistry and Chemical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210009, China.

E-mail: jimin@seu.edu.cn

Abstract

Preclinical Research

The Aurora family of serine/threonine kinases plays important roles in process of cell division or mitosis. Overexpression of Aurora A, B, and C has been identified in many human cancers including colon carcinoma cells. To date, a number of small molecular inhibitors have been developed for reducing Aurora kinases activities of tumor cells in preclinical and clinical trials. In this study, we describe the properties of AM-005, a novel and orally active Aurora A/B kinase inhibitor. AM-005 irreversibly inhibited the proliferation and levels of phospho-Histone H3 in human colon carcinoma cell lines. Defective mitosis was also visualized in AM-005-treated HT29 cells by microscopy. Flow cytometric analysis showed that AM-005 induced the accumulation of HT29 cells with >4N DNA content in a time or concentration-dependent manner, and HT29 cells underwent severe apoptosis at 72 h. Moreover, AM-005 given intragastrically led to suppression of the proliferative response in the xenograft model of colon carcinoma. These results indicate the utility of AM-005 as a promising noncytotoxic agent for treating human colon carcinoma.

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