Effects of the Aurora kinases pan-inhibitor SNS-314 mesylate on anaplastic thyroid cancer derived cell lines.
Clin Ter
; 163(5): e307-13, 2012.
Article
em En
| MEDLINE
| ID: mdl-23099978
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 ANDMETHODS:
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 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.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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Compostos de Fenilureia
/
Tiazóis
/
Neoplasias da Glândula Tireoide
/
Células Tumorais Cultivadas
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article