Dual effects of ouabain, digoxin and proscillaridin A on the regulation of apoptosis in human fibroblasts.
In this study, we looked at the effect of ouabain, digoxin and proscillaridin A on human fibroblasts. These data show that low concentrations of ouabain, digoxin and proscillaridin A can activate proliferation of human fibroblasts, suggesting that the Na+, K+-adenosine triphosphatase complex may act as a transducing receptor. It was shown that 30 nM ouabain, digoxin and proscillaridin A stimulated an antiapoptotic action by the increase in the level of phosphorylated extracellular signal-regulated kinases (P-ERK 1/2). Ouabain, digoxin and proscillaridin A only at the relatively high concentration of 300 nM increased intracellular Ca2+ concentration, activated caspase-3 and induced apoptosis in human fibroblasts. In terms of reduction in cell viability, antiproliferative and apoptotic activity, these cardiac glycosides rank in the order proscillaridin A >digoxin >ouabain.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Bialystok, 15-222 Bialystok, Poland. kwin@umwb.edu.pl
Katarzyna
K
Winnicka
Krzysztof
K
Bielawski
Anna
A
Bielawska
Wojciech
W
Miltyk
D017209:Apoptosis / Q000187:drug effects*; D004077:Digoxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology*; D011442:Proscillaridin / Q000494:pharmacology*; D015398:Signal Transduction
D010042:Ouabain; D004077:Digoxin; D020929:Mitogen-Activated Protein Kinase Kinases; D011442:Proscillaridin