Abstract
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.
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