title: Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells.
abstract: Facilitated anion transport potentially represents a powerful tool to modulate various cellular functions. However, research into the biological effects of small molecule anionophores is still at an early stage. Here we have used two potent anionophore molecules inspired in the structure of marine metabolites tambjamines to gain insight into the effect induced by these compounds at the cellular level. We show how active anionophores, capable of facilitating the transmembrane transport of chloride and bicarbonate in model phospholipid liposomes, induce acidification of the cytosol and hyperpolarization of plasma cell membranes. We demonstrate how this combined effect can be used against cancer stem cells (CSCs). Hyperpolarization of cell membrane induces cell differentiation and loss of stemness of CSCs leading to effective elimination of this cancer cell subpopulation.
authors.affiliation: Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona , 08007 Barcelona, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Soto-Cerrato
authors.affiliation: Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona , 08007 Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Manuel-Manresa
authors.affiliation: Departmento de Química, Universidad de Burgos , 09001 Burgos, Spain.
authors.forename: Elsa
authors.initials: E
authors.lastname: Hernando
authors.affiliation: Fundación de Investigación Hospital General Universitario de Valencia , 46014 Valencia, Spain.|Department of Pathology, Universitat de València , 46010 Valencia, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Calabuig-Fariñas
authors.affiliation: Centro de Investigación Príncipe Felipe , 46012 Valencia, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Martínez-Romero
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat , 08007 Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Fernández-Dueñas
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat , 08007 Barcelona, Spain.|Department of Neuroscience, Karolinska Institute , 171 77 Solna, Stockholm, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Sahlholm
authors.affiliation: Division of Brain Sciences, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Knöpfel
authors.affiliation: Departmento de Química, Universidad de Burgos , 09001 Burgos, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Valverde
authors.affiliation: Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona , 08007 Barcelona, Spain.
authors.forename: Ananda M
authors.initials: AM
authors.lastname: Rodilla
authors.affiliation: Fundación de Investigación Hospital General Universitario de Valencia , 46014 Valencia, Spain.|Department of Biotechnology, Universitat Politècnica de València , 46022 Valencia, Spain.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Jantus-Lewintre
authors.affiliation: Centro de Investigación Príncipe Felipe , 46012 Valencia, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Farràs
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Facultat de Medicina, IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat , 08007 Barcelona, Spain.|Department of Biochemistry and Microbiology, Faculty of Sciences, University of Ghent , 9000 Gent, Belgium.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.affiliation: Cancer Cell Biology Research Group, Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona , 08007 Barcelona, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pérez-Tomás
authors.affiliation: Departmento de Química, Universidad de Burgos , 09001 Burgos, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Quesada
mesh_terms: D000838:Anions; D017209:Apoptosis / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D017136:Ion Transport; D008081:Liposomes; D008564:Membrane Potentials; D014411:Neoplastic Stem Cells / Q000473:pathology*
chemical_list: D000838:Anions; D008081:Liposomes