Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines
| Autor: | Baldini, E., Sorrenti, S., D Armiento, E., Guaitoli, E., Morrone, S., D Andrea, V., Gnessi, L., Moretti, C., Antonelli, A., Antonio CATANIA, Antoni, E., Ulisse, S. |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Scopus-Elsevier Europe PubMed Central |
| Popis: | Anaplastic thyroid carcinomas (ATC) are highly aggressive tumours unresponsive to any available radio- or chemotherapeutic protocol, with a median survival rate of 4-5 months from the time of diagnosis. We previously demonstrated that ATC are characterized by increased expression of the kinases Aurora-A, -B and -C, involved in the regulation of multiple steps of the mitotic phase. In this study, the in vitro effects of SNS-314 mesylate, a pan-inhibitor of the Aurora kinases, on growth and tumorigenicity of ATC cells were evaluated.The effects of SNS-314 mesylate were assessed on the ATC derived cell lines CAL-62, 8305C, 8505C and BHT-101 by means of cell proliferation assay, immunofluorescence, cytofluorimetry, time lapse microscopy, and colony formation in soft agar.Treatment of the different ATC cells with SNS-314 mesylate inhibited proliferation in a time- and dose-dependent manner, with IC(50) comprised between 2.6 nM and 26.6 nM. CAL-62 cells exposed for 24 h to SNS-314 mesylate 100 nM evidenced a significant augmentation of the apoptotic index. Time-lapse video-microscopy of CAL-62 cells showed that SNS-314 mesylate prevents the completion of mitosis leading to polyploidy. Western blot experiments demonstrated that the auto-phosphorylation of the Aurora kinases as well as histone H3 phosphorylation in CAL-62 treated cells was inhibited. Finally, the drug inhibited colony formation in soft agar of all cell lines.Our results demonstrated that SNS-314 mesylate is capable to efficiently reduce cell growth and tumorigenicity of different ATC derived cell lines suggesting its potential therapeutic value for ATC treatment. |
| Databáze: | OpenAIRE |
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