Epi-reevesioside F inhibits Na+/K+-ATPase, causing cytosolic acidification, Bak activation and apoptosis in glioblastoma

作者: Jui-Ling Hsu , Fan-Lun Liu , Lih-Ching Hsu , Hsun-Shuo Chang , Wohn-Jenn Leu

DOI: 10.18632/ONCOTARGET.4429

关键词:

摘要: Epi-reevesioside F, a new cardiac glycoside isolated from the root of Reevesia formosana, displayed potent activity against glioblastoma cells. F was more than ouabain with IC50 values 27.3±1.7 vs. 48.7±1.8 nM (P < 0.001) and 45.0±3.4 81.3±4.3 in T98 U87 cells, respectively. However, both were ineffective A172 cell line low Na+/K+-ATPase α3 subunit expression. induced cycle arrest at S G2 phases apoptosis. It also an increase intracellular concentration Na+ but not Ca2+, cleavage exposure N-terminus Bak, loss mitochondrial membrane potential, inhibition Akt induction caspase cascades. Potassium supplements significantly inhibited F-induced effects. Notably, caused cytosolic acidification that highly correlated anti-proliferative activity. In summary, data suggest inhibits Na+/K+-ATPase, leading to overload acidification, Bak activation potential. The PI3-kinase/Akt pathway is caspase-dependent apoptosis ultimately triggered F-treated

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