Chloroquine inhibits tumor-related Kv10.1 channel and decreases migration of MDA-MB-231 breast cancer cells in vitro

• Published in: European journal of pharmacology 2019-07, Vol.855, p.262-266
• Main Authors: Valdés-Abadía, Belkis, Morán-Zendejas, Rita, Rangel-Flores, José M., Rodríguez-Menchaca, Aldo A.
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - pathology; Cancer; Cell Line, Tumor; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell migration; Cell Movement - drug effects; Chloroquine; Chloroquine - pharmacology; Cytoplasm - drug effects; Cytoplasm - metabolism; Ether-A-Go-Go Potassium Channels - antagonists & inhibitors; HEK293 Cells; Humans; Patch-clamp; Potassium channel; Potassium Channel Blockers - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2019.05.017

Chloroquine (CQ) is an old antimalarial drug currently being investigated for its anti-tumor properties. As chloroquine has been shown to inhibits several potassium channels, we decided to study its effect on the tumor-related Kv10.1 channel by using patch-clamp electrophysiology and cell migration assays. We found that chloroquine inhibited Kv10.1 channels transiently expressed in HEK-293 cells in a concentration- and voltage-dependent manner acting from the cytoplasmic side of the plasma membrane. Chloroquine also inhibited the outward potassium currents from MDA-MB-231 cells, which are mainly carried through Kv10.1 channels as was confirmed using astemizole. Additionally, chloroquine decreased MDA-MB-231 cell migration in the in vitro scratch wound healing assay. In conclusion, our data suggest that chloroquine decreases MDA-MB-231 cell migration by inhibiting Kv10.1 channels. The inhibition of Kv10.1 channels could represent another mechanism of the antitumoral action of chloroquine, besides autophagy inhibition and tumor vessel normalization.