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Reversine triggers mitotic catastrophe and apoptosis in K562 cells.
Leuk Res. 2016 09; 48:26-31.LR

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+Show Affiliations

Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil. Electronic address: ftraina@fmrp.usp.br.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27447890

Citation

Rodrigues Alves, Ana Paula Nunes, et al. "Reversine Triggers Mitotic Catastrophe and Apoptosis in K562 Cells." Leukemia Research, vol. 48, 2016, pp. 26-31.
Rodrigues Alves AP, Machado-Neto JA, Scheucher PS, et al. Reversine triggers mitotic catastrophe and apoptosis in K562 cells. Leuk Res. 2016;48:26-31.
Rodrigues Alves, A. P., Machado-Neto, J. A., Scheucher, P. S., Paiva, H. H., Simões, B. P., Rego, E. M., & Traina, F. (2016). Reversine triggers mitotic catastrophe and apoptosis in K562 cells. Leukemia Research, 48, 26-31. https://doi.org/10.1016/j.leukres.2016.06.011
Rodrigues Alves AP, et al. Reversine Triggers Mitotic Catastrophe and Apoptosis in K562 Cells. Leuk Res. 2016;48:26-31. PubMed PMID: 27447890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversine triggers mitotic catastrophe and apoptosis in K562 cells. AU - Rodrigues Alves,Ana Paula Nunes, AU - Machado-Neto,João Agostinho, AU - Scheucher,Priscila Santos, AU - Paiva,Helder Henrique, AU - Simões,Belinda Pinto, AU - Rego,Eduardo Magalhães, AU - Traina,Fabiola, Y1 - 2016/07/01/ PY - 2016/01/06/received PY - 2016/05/30/revised PY - 2016/06/30/accepted PY - 2016/7/23/entrez PY - 2016/7/23/pubmed PY - 2017/7/27/medline KW - Apoptosis KW - Aurora kinase B KW - Cell viability KW - Chronic myeloid leukemia KW - Mitotic catastrophe KW - Reversine SP - 26 EP - 31 JF - Leukemia research JO - Leuk. Res. VL - 48 N2 - 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. SN - 1873-5835 UR - https://www.unboundmedicine.com/medline/citation/27447890/Reversine_triggers_mitotic_catastrophe_and_apoptosis_in_K562_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0145-2126(16)30143-6 DB - PRIME DP - Unbound Medicine ER -