title: The Aurora kinase A inhibitor TC-A2317 disrupts mitotic progression and inhibits cancer cell proliferation.
abstract: Mitotic progression is crucial for the maintenance of chromosomal stability. A proper progression is ensured by the activities of multiple kinases. One of these enzymes, the serine/threonine kinase Aurora A, is required for proper mitosis through the regulation of centrosome and spindle assembly. In this study, we functionally characterized a newly developed Aurora kinase A inhibitor, TC-A2317. In human lung cancer cells, TC-A2317 slowed proliferation by causing aberrant formation of centrosome and microtubule spindles and prolonging the duration of mitosis. Abnormal mitotic progression led to accumulation of cells containing micronuclei or multinuclei. Furthermore, TC-A2317-treated cells underwent apoptosis, autophagy or senescence depending on cell type. In addition, TC-A2317 inactivated the spindle assembly checkpoint triggered by paclitaxel, thereby exacerbating mitotic catastrophe. Consistent with this, the expression level of Aurora A in tumors was inversely correlated with survival in lung cancer patients. Collectively, these data suggest that inhibition of Aurora kinase A using TC-A2317 is a promising target for anti-cancer therapeutics.
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Yoo Hong
authors.initials: YH
authors.lastname: Min
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Wootae
authors.initials: W
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 130-701, Republic of Korea.|Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ja-Eun
authors.initials: JE
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy*; D000077192:Adenocarcinoma of Lung; D000631:Aminopyridines / Q000494:pharmacology*; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors*; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D059566:M Phase Cell Cycle Checkpoints; D008938:Mitosis / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D004791:Enzyme Inhibitors; D064096:Aurora Kinase A
keywords: Aurora kinase A; TC-A2317; mitosis; spindle assembly checkpoint