期刊
ORAL ONCOLOGY
卷 44, 期 7, 页码 639-645出版社
ELSEVIER
DOI: 10.1016/j.oraloncology.2007.08.010
关键词
Aur-A; biomarker; molecular target; apoptosis
Mitotic Aurora kinases are required for accurate chromosome segregation during cell. division. Ectopic expression of Aurora-A (Aur-A) kinase results in centrosome amplification, aberrant spindles, and consequent aneuploidy. In the present study, we showed that Aurora kinase inhibitory small molecule VX-680 inhibited histone H3 phosphorylation at Ser10, a known in vivo substrate residue of Aurora kinase, in oral squamous cell. carcinoma (OSCC) KB cells. In addition, monopolar spindle structures, typical. abnormalities induced by inhibition of Aur-A, were generated in VX-680-treated cells. Inhibition of Aurora kinase led to reduced KB cell. growth, as assessed by MTT assay. Western Not analysis revealed that VX-680 caused cleavage of two critical apoptotic associated proteins, PARP and caspase-3. In contrast, expression of cell survival factor Bcl-2 was reduced by VX-680 treatment in a dose-dependent manner. Subsequently, nuclear characteristic of DNA fragmentation, indicative of apoptotic cell. death, was clearly observed in these OSCC cells with Aurora kinase inhibitory VX-680. Taken together, we showed that Aurora kinase inhibitory VX-680 led to apoptotic cell death in OSCC cells, suggesting a novel therapeutic target in oral. cancer. (C) 2007 Elsevier Ltd. All rights reserved.
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