Reversine triggers mitotic catastrophe and apoptosis in K562 cells

Abstract

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm of the hematopoietic stem cell characterized by presence of the oncoprotein BCR-ABL1, which have constitutive tyrosine kinase activity. BCR-ABL1 activation induces aurora kinase A (AURKA) and aurora kinase B (AURKB) expression, which are serine-threonine kinases that play an important function in chromosome alignment, segregation and cytokinesis during mitosis. Acquisition of resistance to tyrosine kinase inhibitors has emerged as a problem for CML patients and the identification of novel targets with an important contribution for CML phenotype is of interest. In the present study, we explored the cellular effects of reversine, an AURKA and AURKB inhibitor, in the BCR-ABL1+ K562 cells. Our results indicate that reversine reduces AURKA and AURKB expression, leads to reduction of cell viability and increased apoptosis in a dose- and time-dependent manner, as well as, induces mitotic catastrophe in K562 cells. Our preclinical study establishes that reversine presents an effective antileukemia activity against K562 cells and provide new insights on anticancer opportunities for CML.

Keywords: Apoptosis; Aurora kinase B; Cell viability; Chronic myeloid leukemia; Mitotic catastrophe; Reversine.