title: 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.
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ana Paula Nunes
authors.initials: AP
authors.lastname: Rodrigues Alves
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: João Agostinho
authors.initials: JA
authors.lastname: Machado-Neto
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Priscila Santos
authors.initials: PS
authors.lastname: Scheucher
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Helder Henrique
authors.initials: HH
authors.lastname: Paiva
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Belinda Pinto
authors.initials: BP
authors.lastname: Simões
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Eduardo Magalhães
authors.initials: EM
authors.lastname: Rego
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil. Electronic address: ftraina@fmrp.usp.br.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008938:Mitosis / Q000187:drug effects*; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors; D011687:Purines / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D009025:Morpholines; D047428:Protein Kinase Inhibitors; D011687:Purines; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; C484369:2-(4-morpholinoanilino)-6-cyclohexylaminopurine
keywords: Apoptosis; Aurora kinase B; Cell viability; Chronic myeloid leukemia; Mitotic catastrophe; Reversine