Antiproliferative activity of monastrol in human adenocarcinoma (MCF-7) and non-tumor (HB4a) breast cells
| Autor: | Lilian Areal Marques, Daniele Sartori, Gláucia Fernanda Rocha D'Epiro, Mário Sérgio Mantovani, Ângelo de Fátima, Simone Cristine Semprebon, Andressa Megumi Niwa, Lúcia Regina Ribeiro |
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| Přispěvatelé: | Universidade Estadual de Londrina (UEL), Universidade Federal de Minas Gerais (UFMG), Universidade Estadual Paulista (Unesp) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Mitotic index HB4a Cell Survival Kinesin 5 Antineoplastic Agents Breast Neoplasms Adenocarcinoma Biology 03 medical and health sciences chemistry.chemical_compound Mitotic Index Humans RNA Messenger Viability assay Mammary Glands Human Cyclin-Dependent Kinase Inhibitor p57 Mitosis Cell Proliferation Pharmacology Dose-Response Relationship Drug Cell growth Thiones General Medicine G1 Phase Cell Cycle Checkpoints Cell biology G2 Phase Cell Cycle Checkpoints Gene Expression Regulation Neoplastic CDKN1A Kinetics Pyrimidines 030104 developmental biology Monastrol chemistry Cell culture Apoptosis MCF-7 Cells Female MCF-7 |
| Zdroj: | Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1432-1912 0028-1298 |
| DOI: | 10.1007/s00210-016-1292-9 |
| Popis: | Made available in DSpace on 2018-11-26T15:37:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-12-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundacao Araucaria, Brazil 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 mu M 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. Univ Estadual Londrina, Dept Biol Geral, Rodovia Celso Garcia CID,PR 445,Km380,Caixa Posta, BR-86057970 Londrina, Parana, Brazil Univ Fed Minas Gerais, Dept Quim, Belo Horizonte, MG, Brazil Univ Estadual Paulista, Dept Patol, Sao Paulo, Brazil Univ Estadual Paulista, Dept Patol, Sao Paulo, Brazil |
| Databáze: | OpenAIRE |
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