Selectivity of cation transport across lipid membranes by the antibiotic salinomycin |
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| Affiliation: | 1. Section on Molecular Transport, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, United States of America;2. Section on Integrative Biophysics, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, United States of America;3. Institute for Soft Matter Synthesis and Metrology, Department of Physics, Georgetown University, Washington, DC 20057, United States of America;1. Fraunhofer Institute for Cell Therapy and Immunology (IZI), Branch Bioanalytics and Bioprocesses (IZI-BB), Am Mühlenberg 13, 14476 Potsdam, Germany;2. Institut für Biochemie und Biologie, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam OT Golm, Germany;3. Technische Universität Berlin, Institute of Biotechnology, Straße des 17. Juni 135, 10623 Berlin, Germany;4. Freie Universität Berlin, Institute of Chemistry and Biochemistry, 14195 Berlin, Germany;5. Faculty of Health Science, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, the Brandenburg Medical School Theodor Fontane and the University of Potsdam, Germany |
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| Abstract: | The ionophoric antibiotic salinomycin is in the phase of preclinical tests against several types of malignant tumors including breast cancer. Notwithstanding, the data on its ion selectivity, although being critical for its therapeutic activity, are rather scarce. In the present work, we studied the ability of salinomycin to exert cation/H+-exchange across artificial bilayer lipid membranes (BLM) by measuring electrical potential on planar BLM in the presence of a protonophore and fluorescence responses of the pH-sensitive dye pyranine entrapped in liposomes. The following order of ion selectivity was obtained by these two methods: K+ > Na+ > Rb+ > Cs+ > Li+. Measurements of the monovalent cation-induced quenching of fluorescence of thallium ions in methanol showed that salinomycin effectively binds potassium and calcium but poorly binds sodium and lithium ions. At high concentrations, salinomycin transports Ca2+ through membranes of liposomes and mitochondria, as measured by using the calcium-sensitive dye Fluo-5 N. The data obtained can be used in the mechanistic studies of the anti-tumor activity of salinomycin and its selective cytotoxicity towards cancer stem cells. |
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