The Na+/K+-ATPase is the Achilles Heel of multi-drug-resistant cancer cells

We recently reported that over-expressed Na+/K+-ATPase α subunits are new important anti-cancer targets. Cardiotonic steroids are the natural ligands of Na+/K+-ATPase and thus potentially potent anti-cancer agents with a novel mechanism of action. We report here that the hemi-synthetic cardenolide 19-hydroxy-2″oxovoruscharin is impressively active in cancer cells expressing diverse forms of multi-drug resistance (MDR) either conferred by the over-expression of selected drug-transporter proteins or induced by a range of chemotherapeutic agents. Together with the inability of tumor cells to acquire resistance to 19-hydroxy-2″oxovoruscharin, our data suggest that this novel compound could be especially applicable to notoriously drug-resistant cancers.