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.