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

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dc.contributor.author Silva, Janaina Peixoto da [UNIFESP]
dc.contributor.author Calgarotto, Andrana K. [UNIFESP]
dc.contributor.author Rocha, Katiucha Karolina [UNIFESP]
dc.contributor.author Santos, Caroline Palmeira dos [UNIFESP]
dc.contributor.author Smaili, Soraya Soubhi [UNIFESP]
dc.contributor.author Pereira, Gustavo Jose da Silva [UNIFESP]
dc.contributor.author Pericole, Fernando Vieira
dc.contributor.author Duarte, Adriana da Silva Santos
dc.contributor.author Saad, Sara Teresinha Olalla [UNIFESP]
dc.contributor.author Bincoletto, Claudia [UNIFESP]
dc.date.accessioned 2020-07-20T16:31:22Z
dc.date.available 2020-07-20T16:31:22Z
dc.date.issued 2018
dc.identifier http://dx.doi.org/10.1016/j.biopha.2018.01.027
dc.identifier.citation Biomedicine & Pharmacotherapy. Issy-Les-Moulineaux, v. 99, p. 237-244, 2018.
dc.identifier.issn 0753-3322
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/55908
dc.description.abstract Although 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.sponsorship Fundacao do Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorship Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorship Novartis
dc.format.extent 237-244
dc.language.iso eng
dc.publisher Elsevier France-Editions Scientifiques Medicales Elsevier
dc.relation.ispartof Biomedicine & Pharmacotherapy
dc.rights Acesso restrito
dc.subject Nilotinib en
dc.subject Lithium en
dc.subject Cell death en
dc.subject Autophagy en
dc.subject Bcr-Abl en
dc.subject GSK-3 beta en
dc.subject Clonogenicity en
dc.subject Leukemia cells en
dc.title Lithium, a classic drug in psychiatry, improves nilotinib-mediated antileukemic effects en
dc.type Artigo
dc.description.affiliation Univ Fed Sao Paulo UNIFESP, EPM, Dept Farmacol, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP, Brazil
dc.description.affiliation Univ Campinas UNICAMP, Hematol & Transfus Med Ctr, Inst Nacl Ciencia & Tecnol Sangue, Hemoctr, Campinas, SP, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo UNIFESP, EPM, Dept Farmacol, Rua Tres de Maio 100, BR-04044020 Sao Paulo, SP, Brazil
dc.description.sponsorshipID FAPESP: 12/51215-4
dc.identifier.doi 10.1016/j.biopha.2018.01.027
dc.description.source Web of Science
dc.identifier.wos WOS:000427436800031
dc.coverage Issy-Les-Moulineaux
dc.citation.volume v. 99



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