title: A new small-molecule Aurora B inhibitor shows antitumor activity in human cancer cell lines.
abstract: The Aurora kinase family, as a group of serine/threonine kinases regulating cell cycles, are frequently overexpressed or amplified in human tumors. Here, we showed that the small molecule S4 could inhibit Aurora kinase in both of biochemincal and cell-based levels. The Aurora B inhibition of S4 treatment inhibited the phosphorylation of Histone H3 at serine 10 in HeLa and SMMC7721 cells. Cell proliferation assay showed that inhibition of Aurora kinase led to reduced cancer cell growth. As assessed in colony formation experiment, S4 blocked the capability of the HeLa cells to develop colonies. Subsequently, S4 treatment blocked the mitotic G2/M-G1 phase progression which is characterized by the accumulations of cells with 4 N DNA content, induced a cell cycle arrest in a pseudo G1 phase and resulted in apoptotic cell death in a dose- and time-dependent manners. Taken together, this Aurora kinase inhibitor S4 induces growth inhibition of cancer cell line.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China, windapple@126.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Chenxiao
authors.initials: C
authors.lastname: Jiang
authors.forename: Xianmei
authors.initials: X
authors.lastname: Yang
authors.forename: Lihuan
authors.initials: L
authors.lastname: Cao
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D047428:Protein Kinase Inhibitors; D064107:Aurora Kinase B