Aurora-A kinase inhibition enhances the cytosine arabinoside-induced cell death in leukemia cells through apoptosis and mitotic catastrophe

Aurora-A (Aur-A) is a centrosome-associated serine/threonine kinase that is overexpressed in various cancers and potentially correlated with chemoresistance. In the Ara-C-sensitive leukemia cell lines, silencing of Aur-A by small interfering RNA transfection led to a significant increase in the Ara-C-induced cell death rate through induction of mitochondria-mediated, caspase-dependent apoptosis. In contrast, combined treatment of the Ara-C-resistant leukemia cell lines with Aur-A siRNA and Ara-C remarkably enhanced the cell death rate via non-caspase-dependent mitotic catastrophe. Taken together, Aur-A inhibition was an effective treatment for both the Ara-C-sensitive and resistant leukemia cells by increasing apoptosis and mitotic catastrophe, respectively. (C) 2010 Elsevier Ireland Ltd. All rights reserved.