Antiproliferative activity of monastrol in human adenocarcinoma (MCF-7) and non-tumor (HB4a) breast cells

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dc.creatorLilian Areal Marques
dc.creatorSimone Cristine Semprebon
dc.creatorAndressa Megumi Niwa
dc.creatorGláucia Fernanda Rocha D'epiro
dc.creatorDaniele Sartori
dc.creatorÂngelo de Fátima
dc.creatorLúcia Regina Ribeiro
dc.creatorMário Sérgio Mantovani
dc.date.accessioned2024-02-28T14:43:02Z
dc.date.accessioned2025-09-09T00:35:12Z
dc.date.available2024-02-28T14:43:02Z
dc.date.issued2016
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.description.sponsorshipOutra Agência
dc.identifier.doihttps://doi.org/10.1007/s00210-016-1292-9
dc.identifier.issn0028-1298
dc.identifier.urihttps://hdl.handle.net/1843/64867
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofNaunyn-Schmiedeberg's Archives of Pharmacology
dc.rightsAcesso Restrito
dc.subjectQuímica
dc.subjectFarmacologia
dc.subjectAgentes antineoplásicos
dc.subjectProteínas celulares
dc.subjectAdenocarcinoma
dc.subjectCitotoxidade de mediação celular
dc.subject.otherMonastrol
dc.subject.otherKinesin 5
dc.subject.otherBreast non-Tumor Cell
dc.subject.otherMCF-7
dc.subject.otherHB4a
dc.titleAntiproliferative activity of monastrol in human adenocarcinoma (MCF-7) and non-tumor (HB4a) breast cells
dc.typeArtigo de periódico
local.citation.epage1288
local.citation.spage1279
local.citation.volume389
local.description.resumoMonastrol is an allosteric inhibitor of the mitotic kinesin Eg5 that exhibits an antiproliferative effect against several cell lines. We investigated the antiproliferative effect of monastrol on human breast adenocarcinoma cells (MCF-7) and mammary epithelial cells (HB4a, non-tumoral). Monastrol treatment decreased cell viability only in MCF-7 tumor cells. Real-time cell growth kinetic analysis showed a decrease in the proliferation of MCF-7 cells exposed to monastrol, while in the HB4a cells, only a concentration of 100 μM was able to induce this effect. In a cell cycle analysis, exposure of MCF-7 cells to monastrol led to an increased population of cells in both the G1 and G2/M phases. In HB4a cells, the proportion of cells in the G2/M phase was increased. Monastrol led to an increased mitotic index in both cell lines. Monastrol was not able to induce cell death by apoptosis in any of the cell lines studied. Gene expression analysis was performed to measure the mRNA levels of cell cycle genes, DNA damage indicator gene, and apoptotic related genes. Treatment with monastrol induced in MCF-7 cells a 5-fold increase in the mRNA levels of the CDKN1A gene, an inhibitor of CDKs related with cell cycle arrest in response a stress stimulus, and a 2-fold decrease in CDKN1C mRNA levels in HB4a cells. These results provide evidence that monastrol has a greater antiproliferative effect on MCF-7 tumor cells compared with non-tumor HB4a cells; however, no selective is observed.
local.identifier.orcidhttps://orcid.org/0000-0002-9857-8681
local.identifier.orcidhttps://orcid.org/0000-0002-7550-8509
local.identifier.orcidhttps://orcid.org/0000-0001-9294-222X
local.identifier.orcidhttps://orcid.org/0000-0002-1151-2613
local.identifier.orcidhttps://orcid.org/0000-0002-0465-9932
local.identifier.orcidhttps://orcid.org/0000-0003-2344-5590
local.identifier.orcidhttps://orcid.org/0000-0001-5268-6508
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://link.springer.com/article/10.1007/s00210-016-1292-9#article-info

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