title: Antiproliferative activity of monastrol in human adenocarcinoma (MCF-7) and non-tumor (HB4a) breast cells.
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.
authors: Departamento de Biologia Geral, Universidade Estadual de Londrina, Rodovia Celso Garcia CID, PR 445, Km 380, Caixa Postal 10011, Londrina, Paraná, CEP: 86057-970, Brazil. lilian.areal.marques@gmail.com.
authors: Lilian Areal
authors: LA
authors: Marques
authors: Departamento de Biologia Geral, Universidade Estadual de Londrina, Rodovia Celso Garcia CID, PR 445, Km 380, Caixa Postal 10011, Londrina, Paraná, CEP: 86057-970, Brazil.
authors: Simone Cristine
authors: SC
authors: Semprebon
authors: Departamento de Biologia Geral, Universidade Estadual de Londrina, Rodovia Celso Garcia CID, PR 445, Km 380, Caixa Postal 10011, Londrina, Paraná, CEP: 86057-970, Brazil.
authors: Andressa Megumi
authors: AM
authors: Niwa
authors: Departamento de Biologia Geral, Universidade Estadual de Londrina, Rodovia Celso Garcia CID, PR 445, Km 380, Caixa Postal 10011, Londrina, Paraná, CEP: 86057-970, Brazil.
authors: Gláucia Fernanda Rocha
authors: GF
authors: D'Epiro
authors: Departamento de Biologia Geral, Universidade Estadual de Londrina, Rodovia Celso Garcia CID, PR 445, Km 380, Caixa Postal 10011, Londrina, Paraná, CEP: 86057-970, Brazil.
authors: Daniele
authors: D
authors: Sartori
authors: Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Ângelo
authors: Â
authors: de Fátima
authors: Departamento de Patologia, Universidade Estadual Paulista Júlio de Mesquita Filho, Botucatu, São Paulo, Brazil.
authors: Lúcia Regina
authors: LR
authors: Ribeiro
authors: Departamento de Biologia Geral, Universidade Estadual de Londrina, Rodovia Celso Garcia CID, PR 445, Km 380, Caixa Postal 10011, Londrina, Paraná, CEP: 86057-970, Brazil.
authors: Mário Sérgio
authors: MS
authors: Mantovani
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007700:Kinetics; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008940:Mitotic Index; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013871:Thiones / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D011743:Pyrimidines; D012333:RNA, Messenger; D013871:Thiones; C400223:monastrol
keywords: CDKN1A; HB4a; Kinesin 5; MCF-7; Monastrol