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 a few months of 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 between 25 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 for 12 h to
VX-680 showed an accumulation of cells with > or =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.