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

• Published in: Journal of biomedical science Vol. 22; no. 1; p. 48
• Main Authors: Kawai, Masaaki, Nakashima, Akio, Kamada, Shinji, Kikkawa, Ushio
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.07.2015; BioMed Central
• Subjects: Animals; Apoptosis - drug effects; Aurora Kinase A - biosynthesis; Aurora Kinase A - genetics; Aurora Kinase B - biosynthesis; Aurora Kinase B - genetics; Breast cancer; Cancer; Cell Proliferation - drug effects; Epidermal growth factor; Female; Gene Expression Regulation, Neoplastic - drug effects; Health aspects; Humans; Kinases; MCF-7 Cells; Mice; Pharmacology; Prevention; Prognosis; Protein Kinase Inhibitors - administration & dosage; Protein kinases; Proteins; Staurosporine - administration & dosage; Staurosporine - analogs & derivatives; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - pathology; Xenograft Model Antitumor Assays; Massachusetts; Japan; California
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-015-0150-2

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. 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. 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.