These two authors contributed equally to this work.
Orally Active Aurora A/B Kinase Inhibitor, AM-005, Suppresses the Growth of Human Colon Carcinoma Cells
Article first published online: 20 MAY 2013
© 2013 Wiley Periodicals, Inc.
Drug Development Research
Volume 74, Issue 4, pages 272–281, June 2013
How to Cite
Zheng, M., Zheng, Y., Xie, L., Chang, W., Gu, N. and Ji, M. (2013), Orally Active Aurora A/B Kinase Inhibitor, AM-005, Suppresses the Growth of Human Colon Carcinoma Cells. Drug Dev. Res., 74: 272–281. doi: 10.1002/ddr.21077
Conflict of interest: The authors declare that they have no conflict of interest.
- Issue published online: 10 JUN 2013
- Article first published online: 20 MAY 2013
- Manuscript Accepted: 5 FEB 2013
- Manuscript Received: 14 JAN 2013
- National Basic Research Program of China. Grant Number: 2011CB933503
- Aurora kinase inhibitor;
- human colon carcinoma;
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.