Anticancer Potential of Phytoconstituents Modulating Na/K ATPase Pump; A Novel Repurposing Strategy

Abstract

Na/K ATPase is a heteromeric protein complex located on the plasma membrane of eukaryotic cells that uses ATP to regulate sodium and potassium transport. It is composed of three subunits, α-subunit, β-subunit and γ-subunit. The α-subunit has four isoforms (α1, α2, α3 and α4). Report says that the α1 sub unit is up regulated in certain cancer types such as renal cell carcinoma, glioma and melanoma. It is well evidenced that there is an elevation of activity observed in malignant cells. Drugs targeting Na/K ATPase induces apoptosis and autophagy in cancer cells. Ouabain, a well-known cardenolide, inhibitor of Na/K ATPase, has also been reported for anticancer potential in neuroblastoma. As most of non-cancer drugs have little or tolerable side effects in human, repositioning of non-cancer drugs for anticancer therapy is an excellent strategy for future anticancer drug development. Based on these facts, the present study was aimed to identify novel inhibitors of Na/K ATPase pump, assuming that the identified inhibitors would have anticancer potential through the inhibition of Na/K ATPase pump.