Facilitated Anion Transport Induces Hyperpolarization of the Cell Membrane That Triggers Differentiation and Cell Death in Cancer Stem Cells

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• 作者：Vanessa Soto-Cerrato ; Pilar Manuel-Manresa ; Elsa Hernando ; Silvia Calabuig-Fari?as ; Alicia Martínez-Romero ; Víctor Fernández-Due?as ; Kristoffer Sahlholm ; Thomas Kn?pfel ; María García-Valverde ; Ananda M. Rodilla ; Eloisa Jantus-Lewintre ; Rosa Farràs ; Francisco Ciruela ; Ricardo Pérez-Tomás ; Roberto Quesada
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：December 23, 2015
• 年：2015
• 卷：137
• 期：50
• 页码：15892-15898
• 全文大小：491K
• ISSN：1520-5126

文摘

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.