Fig. 4

Cardiac glycoside-induced apoptosis in tumor cells. Cardiac glycosides bind to Na⁺-K⁺-ATPase and decrease the membrane potential and increase intracellular Na⁺ and Ca⁺⁺ in certain human cancer cell lines, resulting in activation of calcineurin and transcriptional upregulation of Fas ligand. Cardiac glycosides also suppressthe expression of nuclear factor-kappaB and inhibit DNA topoisomerase II. All of these activities induce apoptosis in human cancer cells