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

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dc.citation.issue4
dc.citation.volume1861
dc.contributor.authorVieira Torquato, Heron F. [UNIFESP]
dc.contributor.authorRibeiro-Filho, Antonio C.
dc.contributor.authorBuri, Marcus V. [UNIFESP]
dc.contributor.authorAraujo Junior, Roberto T. [UNIFESP]
dc.contributor.authorPimenta, Renata [UNIFESP]
dc.contributor.authorde Oliveira, Jose Salvador R. [UNIFESP]
dc.contributor.authorFilho, Valdir C.
dc.contributor.authorMacho, Antonio
dc.contributor.authorParedes-Gamero, Edgar J. [UNIFESP]
dc.contributor.authorde Oliveira Martins, Domingos T.
dc.coverageAmsterdam
dc.date.accessioned2020-07-17T14:02:32Z
dc.date.available2020-07-17T14:02:32Z
dc.date.issued2017
dc.description.abstractBackground: 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.en
dc.description.affiliationFed Univ Mato Grosso UFMT, Fac Med, Dept Basic Sci Hlth, Av Fernando Correa Costa 2367, BR-78060900 Cuiaba, MG, Brazil
dc.description.affiliationUniv Fed Sao Paulo UNIFESP, Dept Biochem, Av Pedro Toledo 669, BR-04039401 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Mogi Das Cruzes, Ctr Interdisciplinar Invest Bioquim, Av Dr Ctindido Xavier Almeida Souza 200, BR-08780911 Mogi Das Cruzes, SP, Brazil
dc.description.affiliationUniv Fed Sao Paulo UNIFESP, Dept Med Hematol, Av Diogo Faria 824, BR-04037002 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Vale Itajai UNIVALI, Chem Pharmaceut Res Ctr, Rua Uruguai,458 Ctr, BR-88302202 Itajai, SC, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP, Dept Biochem, Av Pedro Toledo 669, BR-04039401 Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP, Dept Med Hematol, Av Diogo Faria 824, BR-04037002 Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES/Pro-Amazonia)
dc.description.sponsorshipFundacao de Amparo e Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipInstituto Nacional de Ciencia e Tecnologia em Areas Umidas (INAU/CNPq)
dc.description.sponsorshipIDCNPq: 551737/2010-7
dc.description.sponsorshipIDCAPES/Pro-Amazonia: 23038.000731/2013-56
dc.description.sponsorshipIDFAPESP: 2015/16799-3
dc.description.sponsorshipIDINAU/CNPq: 4.02
dc.format.extent958-967
dc.identifierhttp://dx.doi.org/10.1016/j.bbagen.2017.01.033
dc.identifier.citationBiochimica Et Biophysica Acta-General Subjects. Amsterdam, v. 1861, n. 4, p. 958-967, 2017.
dc.identifier.doi10.1016/j.bbagen.2017.01.033
dc.identifier.issn0304-4165
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54849
dc.identifier.wosWOS:000397366200023
dc.language.isoeng
dc.publisherElsevier Science Bv
dc.relation.ispartofBiochimica Et Biophysica Acta-General Subjects
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectCanthin-6-oneen
dc.subjectCell deathen
dc.subjectCell differentiationen
dc.subjectCell cycle arresten
dc.subjectLeukemiaen
dc.subjectLeukemic stem cellsen
dc.titleCanthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cellsen
dc.typeinfo:eu-repo/semantics/article
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