Synthetic cation transporter targeting cancer stem cells

Abstract

Ionic homeostasis is critical for cells to maintain normal physiological functions, including proliferation, differentiation and apoptosis. Recently, modulating intracellular ion concentrations by synthetic anion transporters has proved to be an important strategy to kill cancer cells. For example, salinomycin, a potassium ionophore, was reported to selectively target breast cancer stem cells with over 100 times efficiency than paclitaxel. Although synthetic cation transporters have advantages of improved pharmacological properties and simplified chemical structures, attempts of using these types of compounds in cancer therapy are rather limited, which may be due to the high molecular weight, structure complexity, and poor selectivity of the existing synthetic cation transporters. Here we report a small synthetic potassium transporter with one aminoxy acid unit exhibits high selectivity for K+ cations over Na + or Cl- ions. We have demonstrated that this potassium transporter can establish membrane potential in liposomes and selectively induce the death of human ovarian cancer stem cells. These preliminary studies suggested the promise of using small aminoxy acid-based potassium transporters as anti-cancer agents.