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KMID : 0043320070300101216
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Archives of Pharmacal Research
2007 Volume.30 No. 10 p.1216 ~ p.1224
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Apoptosis-Mediated Cytotoxicity of Ouabain, Digoxin and Proscillaridin A in the Estrogen Independent MDA-MB-231 Breast Cancer Cells
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Winnicka Katarzyna
Bielawski Krzysztof
Bielawska Anna
Miltyk Wojciech
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Abstract
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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
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KEYWORD
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Cytotoxicity, Apoptosis, Breast cancer, MDA-MB-231 cells, Ouabain, Digoxin, Proscillaridin A
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