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Proposed mechanisms that induce apoptosis in leukemic cells by cardiac glycosides (ouabain). Binding of ouabain to NA+/K+-ATPase activates phospholipase C (PLC) and inositol-1,4,5-triphosphate (IP3), the latter subsequently binds to IP3 receptor of endoplasmic reticulum, releasing calcium ions into cytoplasm. Increased intracellular calcium ions might induce the apoptosis through inhibition of NF-κB-mediated signal transduction and depolarization of mitochondrial outer membrane.
