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

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.