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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0021v1 15/2/559    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Arlot-bonnemains, Y. Articles by Ulisse, S. Search for Related Content PubMed PubMed Citation Articles by Arlot-bonnemains, Y. Articles by Ulisse, S.

Y Arlot-bonnemains, Genetiqué et developpement, CNRS, Rennes, 35043, France
E Baldini, Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
B Martin, Rennes, France
J Delcros, Rennes, France
M Toller, Department of Pathology and Experimental Medicine and Clinic, University of Udine, Udine, Italy
F Curcio, Department of Pathology and Experimental Medicine and Clinic, University of Udine, Udine, Italy
F Ambesi-Impiombato, Department of Pathology and Experimental Medicine and Clinic, University of Udine, Udine, Italy
M D'Armiento, Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy
S Ulisse, Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy

Correspondence: Salvatore Ulisse, Email: salvatore.ulisse{at}uniroma1.it

Abstract

Anaplastic thyroid cancers (ATC) are aggressive tumors, which exhibit cell cycle misregulations leading to uncontrolled cellular proliferation and genomic instability. They fail to respond to chemotherapeutic agents and radiation therapy and most patients die within few months from the diagnosis. In the present study, we evaluated the in vitro effects on ATC cells of VX-680, an inhibitor of the Aurora serine/threonine kinases involved in the regulation of multiple aspects of chromosome segregation and cytokinesis. The effects of VX-680 on proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy were tested on the ATC derived cell lines CAL-62, 8305C, 8505C and BHT-101. Treatment of the different ATC cells with VX-680 inhibited proliferation in a time- and dose-dependent manner, with the IC50 comprised between 25 nM and 150 nM. The VX-680 significantly impaired the ability of the different cell lines to form colonies in soft agar. Analysis of caspase-3 activity showed that VX-680 induced apoptosis in the different cell lines. CAL-62 cells exposed 12 h to VX-680 showed an accumulation of cells with 4N DNA content. Time-lapse analysis demonstrated that VX-680 treated CAL-62 cells exit metaphase without dividing. Moreover, histone H3 phosphorylation was abrogated following VX-680 treatment.

In conclusion, our data demonstrated that VX-680 is effective in reducing cell growth of different ATC derived cell lines and warrant further investigation to exploit its potential therapeutic value for ATC treatment.