Midostaurin preferentially attenuates proliferation of triple-negative breast cancer cell lines through inhibition of Aurora kinase family

Journal of Biomedical Science

Ushio Kikkawa⁴  Shinji Kamada¹  Akio Nakashima²  Masaaki Kawai³ 

[1]Present Address: Research Center for Environmental Genomics, Kobe University, Kobe 657-8501, Japan

[2]Biosignal Research Center, Kobe University, Kobe 657-8501, Japan

[3]Central Research Laboratories, Sysmex Corporation, Kobe 651-2271, Japan

[4]Department of Bioresource Science, Graduate School of Agricultural Science, Kobe University, Kobe 657-8501, Japan

关键词: Aurora kinase;    Clustering analysis;    Midostaurin;    Triple-negative breast cancer;   

Others  :  1219629
DOI  :  10.1186/s12929-015-0150-2

 received in 2014-12-04, accepted in 2015-05-25,  发布年份 2015

【 摘 要 】

Background

Breast cancer is classified into three subtypes by the expression of biomarker receptors such as hormone receptors and human epidermal growth factor receptor 2. Triple-negative breast cancer (TNBC) expresses none of these receptors and has an aggressive phenotype with a poor prognosis, which is insensitive to the drugs that target the hormone receptors and human epidermal growth factor receptor 2. It is, thus, required to develop an effective therapeutic reagent to treat TNBC.

Results

The study using a panel of 19 breast cancer cell lines revealed that midostaurin, a multi-target protein kinase inhibitor, suppresses preferentially the growth of TNBC cells comparing with non-TNBC cells. Clustering analysis of the drug activity data for the panel of cancer cell lines predicted that midostaurin shares the target with Aurora kinase inhibitors. Following studies indicated that midostaurin attenuates the phosphorylation reaction mediated by Aurora kinase in the cells and directly inhibits this protein kinase in vitro, and that this reagent induces apoptosis accompanying accumulation of 4N and 8N DNA cells in TNBC cells.

Conclusion

Midostaurin suppresses the proliferation of TNBC cells among the breast cancer cell lines presumably through the inhibition of the Aurora kinase family. The precise study of midostaurin on cell growth will contribute to the development of the drug for the treatment of TNBC.

【 授权许可】

   
2015 Kawai et al.

【 图 表 】

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