Chloroquine inhibits tumor-related Kv10.1 channel and decreases migration of MDA-MB-231 breast cancer cells in vitro
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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. © 2019 Elsevier B.V.
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Cancer; Cell migration; Chloroquine; Patch-clamp; Potassium channel astemizole; chloroquine; potassium channel; potassium channel Kv10.1; unclassified drug; chloroquine; KCNH1 protein, human; potassium channel blocking agent; potassium channel HERG; antineoplastic activity; Article; autophagy; breast cancer; cancer inhibition; cell membrane; cell migration; cell migration assay; cell surface; controlled study; drug effect; embryo; HEK293 cell line; human; human cell; in vitro study; MDA-MB-231 cell line; patch clamp technique; priority journal; protein expression; wound healing assay; breast tumor; cell motion; cytoplasm; metabolism; pathology; tumor cell line; Breast Neoplasms; Cell Line, Tumor; Cell Membrane; Cell Movement; Chloroquine; Cytoplasm; Ether-A-Go-Go Potassium Channels; HEK293 Cells; Humans; Potassium Channel Blockers
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