Cardiac Glycosides as Novel Cancer Therapeutic Agents

Relative human and rodent tumor cell sensitivity to oleandrin correlates with Na⁺,K⁺-ATPase subunit composition. A. Mouse pancreatic cancer cells that lack expression of the α-3 subunit (Panc-02) are non-responsive to oleandrin whereas human tumor cell lines MiaPaca and Panc-1 (that contain high expression of α-3 relative to α-1) are extremely responsive. The human pancreatic tumor cell line BXPC3 that contains a very low level of the α-3 subunit, as per immunoblot analysis (B), is somewhat resistant to cytotoxic effects of oleandrin. These data suggest that it is the lack of α 3 in rodent tumor cell lines that explains their resistance to cardiac glycosides. In addition, the data suggest that it is the relative α 3:α 1 ratio correlates with human tumor cell sensitivity to lipid soluble cardiac glycosides such as oleandrin.