A Novel Investigation of Potassium Transport in Breast Cancer Cells

Studies have shown cardiac glycosides (CG) produce specific antiproliferative effects in cancer cells through unidentified mechanisms. Known to induce their effects via the Na‐K ATPase (NaK), we hypothesize CGs inhibit cancer cell growth through NaK‐mediated mechanisms. We used four breast cancer cell lines (MCF7, T47D, MDA453, MDA231) and a control breast cell line (MCF10A). First we determined optimum concentration at which ouabain inhibits cancer growth by incorporation of bromodeoxyuridine into newly synthesized DNA. Treatment with 100nM ouabain had no effect on MCF10A cells but decreased proliferation of cancer cells. We also defined the expression and function of the NaK by western blot and Rb‐uptake. MDA453 cells do not express any subunits of NaK while all others express á1, á3 and â1. Despite the absence of NaK, MDA453 cells exhibit 3 fold higher Rb+ flux than all other cell lines. Further studies showed that H‐K ATPase contributes to 50% of the flux in MDA543 cells but not NKCC. We conclude that utility of cardiac glycosides as chemotherapeutic seems to be limited and cancer cells may alter expression of K+ transporters that serve as better therapeutic targets. Funds: AHA