The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1

Background2-hydroxyoleic acid (2OHOA) is a synthetic fatty acid with antitumor properties that alters membrane composition and structure, which in turn influences the functioning of membrane proteins and cell signaling. In this study, we propose a novel antitumoral mechanism of 2OHOA accomplished through the regulation of Kv10.1 channels. We evaluated the effects of 2OHOA on Kv10.1 channels expressed in HEK-293 cells by using electrophysiological techniques and a cell proliferation assay.Results2OHOA increased Kv10.1 channel currents in a voltage-dependent manner, shifted its conductance-voltage relationship towards negative potentials, and accelerated its activation kinetics. Moreover, 2OHOA reduced proliferation of cells that exogenously (HEK-293) and endogenously (MCF-7) expressed Kv10.1 channels. It is worth noting that the antiproliferative effect of 2OHOA was maintained in HEK-293 cells expressing a non-conducting mutant of Kv10.1 channel (Kv10.1-F456A), while it did not affect HEK-293 cells not expressing Kv10.1 channels, suggesting that 2OHOA interferes with a non-conducting function of Kv10.1 channels involved in cell proliferation. Finally, we found that 2OHOA can act synergistically with astemizole, a Kv10.1 channel blocker, to decrease cell proliferation more efficiently.ConclusionOur data suggest that 2OHOA decreases cell proliferation, at least in part, by regulating Kv10.1 channels.

Automated summary

In this study, it was found that 2-hydroxyoleic acid (2OHOA) decreases cell proliferation by regulating Kv10.1 channels, suggesting its potential as an antitumoral agent.