title: Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells.
abstract: The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin.
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Estadual de Londrina-CCB-BIO, Campus Universitário-Caixa Postal 10011, Rodovia Celso Garcia Cid (PR-445), Km 380, Londrina, Paraná, CEP 86057-970, Brazil.
authors.forename: Andressa Megumi
authors.initials: AM
authors.lastname: Niwa
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Estadual de Londrina-CCB-BIO, Campus Universitário-Caixa Postal 10011, Rodovia Celso Garcia Cid (PR-445), Km 380, Londrina, Paraná, CEP 86057-970, Brazil.
authors.forename: Gláucia Fernanda Rocha
authors.initials: GF
authors.lastname: D Epiro
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Estadual de Londrina-CCB-BIO, Campus Universitário-Caixa Postal 10011, Rodovia Celso Garcia Cid (PR-445), Km 380, Londrina, Paraná, CEP 86057-970, Brazil.
authors.forename: Lilian Areal
authors.initials: LA
authors.lastname: Marques
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Estadual de Londrina-CCB-BIO, Campus Universitário-Caixa Postal 10011, Rodovia Celso Garcia Cid (PR-445), Km 380, Londrina, Paraná, CEP 86057-970, Brazil.
authors.forename: Simone Cristine
authors.initials: SC
authors.lastname: Semprebon
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Estadual de Londrina-CCB-BIO, Campus Universitário-Caixa Postal 10011, Rodovia Celso Garcia Cid (PR-445), Km 380, Londrina, Paraná, CEP 86057-970, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Sartori
authors.affiliation: Departamento de Patologia, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Lúcia Regina
authors.initials: LR
authors.lastname: Ribeiro
authors.affiliation: Laboratório de Genética Toxicológica, Universidade Estadual de Londrina-CCB-BIO, Campus Universitário-Caixa Postal 10011, Rodovia Celso Garcia Cid (PR-445), Km 380, Londrina, Paraná, CEP 86057-970, Brazil. biomsm@uel.br.
authors.forename: Mário Sérgio
authors.initials: MS
authors.lastname: Mantovani
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011714:Pyrans / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Apoptosis; Cancer; Cytotoxicity; Genotoxicity; Salinomycin