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Orally Active A urora A / B Kinase Inhibitor, AM ‐005, Suppresses the Growth of Human Colon Carcinoma Cells
Author(s) -
Zheng Ming,
Zheng Youguang,
Xie Li,
Chang Weiwei,
Gu Ning,
Ji Min
Publication year - 2013
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21077
Subject(s) - mitosis , kinase , cancer research , carcinoma , apoptosis , cell growth , threonine , cell division , flow cytometry , cell culture , biology , serine , phosphorylation , cell , chemistry , medicine , microbiology and biotechnology , immunology , biochemistry , genetics
Preclinical ResearchThe A urora family of serine/threonine kinases plays important roles in process of cell division or mitosis. Overexpression of A urora 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 A urora 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 A urora A / B kinase inhibitor. AM ‐005 irreversibly inhibited the proliferation and levels of phospho‐ H istone H 3 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.