Ouabain inhibits Wnt/β-catenin signaling and induces cytotoxicity in cancer cells

Abstract

Ouabain, a cardiac glycoside found in plants, is primarily used in the treatment of congestive heart failure and arrhythmia. Recently ouabain has been shown to exert anticancer effects, but the underlying mechanism is not clear. Aberrant activation of the Wnt/β-catenin signaling cascade is associated with numerous human cancers. In this study, we identified ouabain as a potent inhibitor of the Wnt/β-catenin signaling pathway by targeting the low density lipoprotein-receptor-related protein 6 (LRP6) and β-catenin. In colon cancer HCT116 and non-small cell lung cancer A549 cells, nanomolar concentrations of ouabain significantly decreased the levels of phosphorylated LRP6, total LRP6, active β-catenin and β-catenin. In addition, ouabain inhibited β-catenin-stimulated Wnt target gene expression, including expression of CD44 and fibronection . Furthermore, ouabain reduced the viability of HCT116 and A549 cells and induced apoptosis in both cell lines. This study clarified the molecular mechanism underlying anti-cancer activity of ouabain through blocking the Wnt/β-catenin signaling pathway.