Apoptosis-mediated cytotoxicity of ouabain, digoxin and proscillaridin A in the estrogen independent MDA-MB-231 breast cancer cells.
We examined the effects of three cardiac glycosides, ouabain, digoxin and proscillaridin A, on the proliferation of estrogen independent MDA-MB-231 breast cancer cells. In terms of reduction in cell viability, the compounds rank for both 24 h and 48 h of incubation in MDA-MB-231 cells in the order proscillaridin A > digoxin > ouabain. Digoxin for 24 h and 48 h of incubation in MDA-MB-231 cells proved to be only slightly more potent than ouabain, with IC50 values of 122 +/- 2 and 70 +/- 2 nM, respectively, compared to 150 +/- 2 and 90 +/- 2 nM for ouabain. In contrast, proscillaridin A, was much more active and showed a high level of cytotoxic potency, IC50 51 +/- 2 and 15 +/- 2 nM for 24 h and 48 h of incubation, respectively. The concentrations of digoxin, ouabain and proscillaridin A needed to inhibit [3H]thymidine incorporation into DNA by 50% (IC50) in MDA-MB-231 cells for 24 h of incubation were found to be 124 +/- 2 nM, 142 +/- 2 nM, and 48 +/- 2 nM, respectively. In the present study, we demonstrated that ouabain, digoxin, and proscillaridin A induce apoptosis in MDA-MB-231 cells by increasing free calcium concentration and by activating caspase-3.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University in Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland. kwin@amb.edu.pl
Katarzyna
K
Winnicka
Krzysztof
K
Bielawski
Anna
A
Bielawska
Wojciech
W
Miltyk
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004077:Digoxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D010042:Ouabain / Q000494:pharmacology*; D011442:Proscillaridin / Q000494:pharmacology*; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D010042:Ouabain; D004077:Digoxin; D053148:Caspase 3; D011442:Proscillaridin; D002118:Calcium