Effects of KRC-108 on the Aurora A activity and growth of 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.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Hye Jin
HJ
Chung
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Kyeong Ryang
KR
Park
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Hyo Jeong
HJ
Lee
College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea.
Jongkook
J
Lee
School of Life Sciences, Gwangju Institute of Science & Technology, Gwangju, Republic of Korea.
Jeong-Hyun
JH
Kim
School of Life Sciences, Gwangju Institute of Science & Technology, Gwangju, Republic of Korea.
Yong-Chul
YC
Kim
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea. Electronic address: syhan@gnu.ac.kr.
Sun-Young
SY
Han
D000631:Aminopyridines / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A / Q000378:metabolism*; D001583:Benzoxazoles / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007928:Lethal Dose 50
D000631:Aminopyridines; D001583:Benzoxazoles; C572621:KRC-108; C576920:Aurka protein, rat; D064096:Aurora Kinase A
Aminopyridine derivatives; Apoptosis; Aurora A kinase; Colorectal cancer