title: Aurora kinase small molecule inhibitor destroys mitotic spindle, suppresses cell growth, and induces apoptosis in oral squamous cancer cells.
abstract: 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 blot 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.
authors.affiliation: Department of Maxillofacial Surgery, Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Caobing
authors.initials: C
authors.lastname: Pan
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.forename: Jine
authors.initials: J
authors.lastname: Yao
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Zijie
authors.initials: Z
authors.lastname: Long
authors.forename: Hongzhang
authors.initials: H
authors.lastname: Huang
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000782:Aneuploidy; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A; D064127:Aurora Kinases; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D008941:Spindle Apparatus / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines
chemical_list: D000970:Antineoplastic Agents; D064096:Aurora Kinase A; D064127:Aurora Kinases; D053148:Caspase 3; D010879:Piperazines; D017346:Protein Serine-Threonine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; C484810:tozasertib; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines; C576918:Aurka protein, mouse