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Eur J Med Chem. 2015 Jan 7;89:310-9. doi: 10.1016/j.ejmech.2014.10.044. Epub 2014 Oct 16.

In vitro and in vivo characterization of a benzofuran derivative, a potential anticancer agent, as a novel Aurora B kinase inhibitor.

Author information

1
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
2
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China; Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA, USA.
3
Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA; College of Life Sciences, Southwest University, Chongqing, PR China.
4
Abbott Shanghai R&D Center, Shanghai, PR China.
5
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China. Electronic address: longyu@fudan.edu.cn.

Abstract

Aurora B is a serine/threonine kinase that has a key role in mitosis and is overexpressed in cancer cells. Aberrations in Aurora B are highly correlated with tumorigenesis and cancer development, so many studies have focused on the development of Aurora B kinase inhibitors. Based on one of our previous high-throughput screening studies, we identified lead compound S6, a small-molecule benzofuran derivative that binds Aurora B and inhibits its kinase activity in vitro. S6 also displayed high selectivity for Aurora B inhibition. The cytotoxicity of S6 was assessed against a panel of 21 cancer cell lines. The cervical cancer cell line HeLa, liver cancer cell line HepG2 and colon cancer cell line SW620 were the most sensitive to S6 treatment. We found that S6 decreased the proliferation and colony formation of these three cell lines and elevated their percentages of cells in the G2/M phase of the cell cycle. S6 also inhibited phospho-histone H3 on Ser 10, a natural biomarker of endogenous Aurora B activity. The growth suppression of liver cancer QGY-7401 xenograft tumors was observed in nude mice after S6 administration, and this effect was accompanied by the in vivo inhibition of phospho-histone H3 (Ser 10). Taken together, we conclude that targeting Aurora B with compound S6 may be a novel strategy for cancer treatment, and additional studies are warranted.

KEYWORDS:

Aurora B; Compound S6, (2Z)-2-(3, 4-dihydroxybenzylidene)-1-benzofuran-3(2H)-one (CID:3325808); Kinase inhibitor; Molecular targeted chemotherapy; Tumor growth

PMID:
25462247
DOI:
10.1016/j.ejmech.2014.10.044
[Indexed for MEDLINE]

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