Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/64867
Type: Artigo de Periódico
Title: Antiproliferative activity of monastrol in human adenocarcinoma (MCF-7) and non-tumor (HB4a) breast cells
Authors: Lilian Areal Marques
Simone Cristine Semprebon
Andressa Megumi Niwa
Gláucia Fernanda Rocha D'epiro
Daniele Sartori
Ângelo de Fátima
Lúcia Regina Ribeiro
Mário Sérgio Mantovani
Abstract: Monastrol 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.
Subject: Química
Farmacologia
Agentes antineoplásicos
Proteínas celulares
Adenocarcinoma
Citotoxidade de mediação celular
language: eng
metadata.dc.publisher.country: Brasil
Publisher: Universidade Federal de Minas Gerais
Publisher Initials: UFMG
metadata.dc.publisher.department: ICX - DEPARTAMENTO DE QUÍMICA
Rights: Acesso Restrito
metadata.dc.identifier.doi: https://doi.org/10.1007/s00210-016-1292-9
URI: http://hdl.handle.net/1843/64867
Issue Date: 2016
metadata.dc.url.externa: https://link.springer.com/article/10.1007/s00210-016-1292-9#article-info
metadata.dc.relation.ispartof: Naunyn-Schmiedeberg's Archives of Pharmacology
Appears in Collections:Artigo de Periódico

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