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

Repositioning the drugs through poly-pharmacological approaches, including cancer therapy is gaining scientific interest, as many non-cancer targeting drugs have well-established safety profile but unexplored for its potential to combat cancer. The complex heterotrimeric protein Na+/K+ ATPase (NKA) is complex. It is existing on the plasma membrane of eukaryotic cells and makes use of ATP for the maintenance of sodium and potassium transport. It has three subunits, α, β and γ. The α-subunit has four isoforms namely α1, α2, α3, and α4. One of the published studies reports that the α1 subunit is over expressed and activated in certain malignancies like renal cell carcinoma, glioma, and melanoma. Thus, it is hypothesized that NKA has unique roles in cancer cell growth and development. For instance, Ouabain is a well-known inhibitor of NKA which is used primarily as a cardiac stimulant has also been recently reported for its potential anticancer properties in neuroblastoma cells. Consequently, the search for the molecules which has the potential to inhibit specific NKA in cancer cells gaining tremendous scientific attention. Recently perillyl alcohol has been reported for anticancer potential through NKA inhibition. Sinceperillyl alcohol has a cyclic ring in its structural frame, we opted the similar chemical signatures of Phyto terpenes and phytotannins of for our study. Thus, the present study opted for scaffold repurposing strategy using in-silico methods to identify and screen some of the well-known phytocompounds for its possible anticancer effects by inhibiting NKA.