Effects of KRC-108 on the Aurora A activity and growth of colorectal cancer cells

• A novel aminopyridine derivative, KRC-108 inhibits Aurora A activity.
• Aurora A inhibition by KRC-108 induces arrest of cells in G2/M phase and apoptosis.
• KRC-108 inhibits migration and colony growth of human colorectal cancer cells.

Aurora A is involved in regulating multiple steps of mitosis. Over-expression of Aurora A is related to tumorigenesis and poor prognosis. KRC-108 is a novel multi-kinase inhibitor which has anti-tumor activity in vivo. In this study, we identified the inhibitory effects of KRC-108 on Aurora A kinase and growth-inhibitory characteristics of KRC-108. The in vitro kinase activity assay, immunoblot, and immunofluorescence analyses demonstrated that KRC-108 inhibited Aurora A activity. KRC-108 exhibited cytotoxicity against human colorectal cancer cell line HT-29. Colony formation assays showed that KRC-108 reduced the colony growth of HT-29 cells. KRC-108 also inhibited migration of HT-29 cells. The expression levels of cyclin B1 and CDC2 were decreased by KRC-108 in HT-29 cells. Cell cycle analysis and flow cytometry indicated that the inhibitory effects of KRC-108 on cell growth are due to induction of G2/M arrest and apoptosis by inhibition of Aurora A. KRC-108 induces cell-cycle arrest and apoptosis in colorectal cancer cell line by Aurora A inhibition. The reported in vivo anti-tumor effects of KRC-108 might partly be due to anti-Aurora A effects. This study suggests that KRC-108 has potential for development as an anti-tumor agent, although further studies are needed.