Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells

Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells

Author Vieira Torquato, Heron F. Autor UNIFESP Google Scholar
Ribeiro-Filho, Antonio C. Google Scholar
Buri, Marcus V. Autor UNIFESP Google Scholar
Araujo Junior, Roberto T. Autor UNIFESP Google Scholar
Pimenta, Renata Autor UNIFESP Google Scholar
de Oliveira, Jose Salvador R. Autor UNIFESP Google Scholar
Filho, Valdir C. Google Scholar
Macho, Antonio Google Scholar
Paredes-Gamero, Edgar J. Autor UNIFESP Google Scholar
de Oliveira Martins, Domingos T. Google Scholar
Abstract Background: Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. Methods: Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin(+)) and leukemia stem cell population (CD34(+) CD38(-)Lin(-/low) Results: Among the human lineages tested, Kasumi-1 was the most sensitive to canthin-6-one. Canthin-6-one induced cell death with apoptotic (caspase activation, decrease of mitochondrial potential) and necrotic (lysosomal permeabilization, double labeling of annexin V/propidium iodide) characteristics. Moreover, canthin-6-one induced cell cycle arrest at Go/Gi (7 mu M) and G2 (45 mu m) evidenced by DNA content, BrdU incorporation and cyclin Bl/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11 b and CD15) and the transcription factor PU.1. Furthermore, a reduction of the leukemic stem cell population and clonogenic capability of stem cells were observed. Conclusions: These results show that canthin-6-one can affect Kasumi-1 cells by promoting cell death, cell cycle arrest and cell differentiation depending on concentration used. General significance: Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity. (C) 2017 Elsevier B.V. All rights reserved.
Keywords Canthin-6-one
Cell death
Cell differentiation
Cell cycle arrest
Leukemic stem cells
xmlui.dri2xhtml.METS-1.0.item-coverage Amsterdam
Language English
Sponsor Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES/Pro-Amazonia)
Fundacao de Amparo e Pesquisa do Estado de Sao Paulo (FAPESP)
Instituto Nacional de Ciencia e Tecnologia em Areas Umidas (INAU/CNPq)
Grant number CNPq: 551737/2010-7
CAPES/Pro-Amazonia: 23038.000731/2013-56
FAPESP: 2015/16799-3
INAU/CNPq: 4.02
Date 2017
Published in Biochimica Et Biophysica Acta-General Subjects. Amsterdam, v. 1861, n. 4, p. 958-967, 2017.
ISSN 0304-4165 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 958-967
Access rights Closed access
Type Article
Web of Science ID WOS:000397366200023

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