Deregulated expression of the
Aurora kinases (Aurora-A, B, and C) is thought to be involved in cell malignant transformation and
genomic instability in several
cancer types. Over the last decade, a number of small-molecule inhibitors of
Aurora kinases have been developed, which have proved to efficiently restrain malignant cell growth and tumorigenicity. Regarding medullary
thyroid carcinoma (MTC), we previously showed the efficacy of a pan-
Aurora kinase inhibitor (MK-0457) in impairing growth and survival of the MTC-derived cell line TT. In the present study, we sought to establish if one of the
Aurora kinases might represent a preferential target for MTC
therapy. The effects of selective inhibitors of Aurora-A (
MLN8237) and Aurora-B (
AZD1152) were analyzed on TT cell proliferation, apoptosis, cell cycle, and ploidy. The two inhibitors reduced TT cell proliferation in a time- and dose-dependent manner, with IC50 of 19.0 ± 2.4 nM for
MLN8237 and 401.6 ± 44.1 nM for
AZD1152. Immunofluorescence experiments confirmed that
AZD1152 inhibited phosphorylation of
histone H3 (Ser10) by Aurora-B, while it did not affect Aurora-A autophosphorylation.
MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Cytofluorimetry experiments showed that both inhibitors induced accumulation of cells in G2/M phase and increased the subG0/G1 fraction and
polyploidy. Finally, both inhibitors triggered apoptosis. We demonstrated that inhibition of either Aurora-A or Aurora-B has antiproliferative effects on TT cells, and thus it would be worthwhile to further investigate the therapeutical potential of
Aurora kinase inhibitors in MTC treatment.