Objectives: 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. Materials and Methods: 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. Results: Treatment of the different ATC cells with SNS-314 mesylate inhibited proliferation in a time- and dose-dependent manner, with IC50 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. Conclusions: 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. © Società Editrice Universo (SEU).

Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines / Baldini, Enke; Sorrenti, Salvatore; E., D'Armiento; Guaitoli, Eleonora; Morrone, Stefania; D'Andrea, Vito; Gnessi, Lucio; C., Moretti; A., Antonelli; Catania, Antonio; DE ANTONI, Enrico; Ulisse, Salvatore. - In: LA CLINICA TERAPEUTICA. - ISSN 0009-9074. - ELETTRONICO. - 163:5(2012), pp. e307-e313.

Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines

BALDINI, ENKE;SORRENTI, Salvatore;GUAITOLI, ELEONORA;MORRONE, Stefania;D'ANDREA, Vito;GNESSI, Lucio;CATANIA, Antonio;DE ANTONI, Enrico;ULISSE, SALVATORE
2012

Abstract

Objectives: 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. Materials and Methods: 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. Results: Treatment of the different ATC cells with SNS-314 mesylate inhibited proliferation in a time- and dose-dependent manner, with IC50 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. Conclusions: 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. © Società Editrice Universo (SEU).
2012
mitosis; anaplastic thyroid cancer; aurora kinases; thyroid cancer; sns-314 mesylate; cell cycle; aneuploidy; cell lines
01 Pubblicazione su rivista::01a Articolo in rivista
Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines / Baldini, Enke; Sorrenti, Salvatore; E., D'Armiento; Guaitoli, Eleonora; Morrone, Stefania; D'Andrea, Vito; Gnessi, Lucio; C., Moretti; A., Antonelli; Catania, Antonio; DE ANTONI, Enrico; Ulisse, Salvatore. - In: LA CLINICA TERAPEUTICA. - ISSN 0009-9074. - ELETTRONICO. - 163:5(2012), pp. e307-e313.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/483966
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