Oleandrin induces apoptosis in human, but not in murine cells: dephosphorylation of Akt, expression of FasL, and alteration of membrane fluidity.

摘要: Common practice to evaluate the efficacy of any compound as drug is done in cell-based vitro system followed by vivo murine model prior clinical trial human. Cardiac glycosides are very effective kill human cells, but not cells. In this report, we describe comparative molecular mechanism oleandrin, a cardiac glycoside action and Treatment with oleandrin facilitated nuclear translocation FKHR human, cells dephosphorylating Akt. It activated MAPK JNK also induced expression FasL leads apoptosis detected assaying caspases activation, PARP cleavage, fragmentation, annexin staining. Oleandrin interacted plasma membrane evaluated HPLC, altered its fluidity DPH binding, inhibited Na+/K+-ATPase activity, increased intracellular free Ca2+ level calcineurin activity only Results suggest that might be different than murine, which interact disturb pump resulting calcification induction Ca2+-dependent cellular responses such apoptosis.