The Na+/K+-ATPase is the Achilles heel of multi-drug-resistant cancer cells.
We recently reported that over-expressed Na(+)/K(+)-ATPase alpha 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.
Mijatovic
Tatjana
T
Unibioscreen SA, Brussels, Belgium.
Jungwirth
Ute
U
Heffeter
Petra
P
Hoda
Mir Ali Reza
MA
Dornetshuber
Rita
R
Kiss
Robert
R
Berger
Walter
W