Lithium, a classic drug in psychiatry, improves nilotinib-mediated antileukemic effects

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dc.citation.volumev. 99
dc.contributor.authorSilva, Janaina Peixoto da [UNIFESP]
dc.contributor.authorCalgarotto, Andrana K. [UNIFESP]
dc.contributor.authorRocha, Katiucha Karolina [UNIFESP]
dc.contributor.authorSantos, Caroline Palmeira dos [UNIFESP]
dc.contributor.authorSmaili, Soraya Soubhi [UNIFESP]
dc.contributor.authorPereira, Gustavo Jose da Silva [UNIFESP]
dc.contributor.authorPericole, Fernando Vieira
dc.contributor.authorDuarte, Adriana da Silva Santos
dc.contributor.authorSaad, Sara Teresinha Olalla [UNIFESP]
dc.contributor.authorBincoletto, Claudia [UNIFESP]
dc.coverageIssy-Les-Moulineaux
dc.date.accessioned2020-07-20T16:31:22Z
dc.date.available2020-07-20T16:31:22Z
dc.date.issued2018
dc.description.abstractAlthough Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3 beta phosphorylation and Bcr-Abl oncoprotein levels reduction. Interestingly, these events were related to autophagy induction, expressed by increased LC3II protein levels in the group treated with L + N. Furthermore, the clonogenic capacity of progenitor cells from CML patients was drastically reduced by L + N, as well as lithium and nilotinib when used separately. The number of cell aggregates (clusters), were increased by all treatments (L + N, lithium, and nilotinib). This pioneering research has demonstrated that lithium might be of therapeutic value when targeting Bcr-Abl cells with nilotinib because it triggers cell death in addition to exerting classical antiproliferative effects, opening new perspectives for novel target and therapeutic approaches to eradicate CML.en
dc.description.affiliationUniv Fed Sao Paulo UNIFESP, EPM, Dept Farmacol, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Campinas UNICAMP, Hematol & Transfus Med Ctr, Inst Nacl Ciencia & Tecnol Sangue, Hemoctr, Campinas, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo UNIFESP, EPM, Dept Farmacol, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao do Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipNovartis
dc.description.sponsorshipIDFAPESP: 12/51215-4
dc.format.extent237-244
dc.identifierhttp://dx.doi.org/10.1016/j.biopha.2018.01.027
dc.identifier.citationBiomedicine & Pharmacotherapy. Issy-Les-Moulineaux, v. 99, p. 237-244, 2018.
dc.identifier.doi10.1016/j.biopha.2018.01.027
dc.identifier.issn0753-3322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55908
dc.identifier.wosWOS:000427436800031
dc.language.isoeng
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevier
dc.relation.ispartofBiomedicine & Pharmacotherapy
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectNilotiniben
dc.subjectLithiumen
dc.subjectCell deathen
dc.subjectAutophagyen
dc.subjectBcr-Ablen
dc.subjectGSK-3 betaen
dc.subjectClonogenicityen
dc.subjectLeukemia cellsen
dc.titleLithium, a classic drug in psychiatry, improves nilotinib-mediated antileukemic effectsen
dc.typeinfo:eu-repo/semantics/article
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