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Winnicka, Katarzyna,Bielawski, Krzysztof,Bielawska, Anna,Miltyk, Wojciech 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.10
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 hand 48 h of incubation in MDA-MB-231 cells in the order proscillaridin A > digoxin > ouabain. Digoxin for 24 hand 48 h of incubation in MDA-MB-231 cells proved to be only slightly more potent than ouabain, with $IC_{50}$ values of $122{\pm}2\;and\;70{\pm}2nM$, respectively, compared to $150{\pm}2\;and\;90{\pm}2nM$ for ouabain. In contrast, proscillaridin A, was much more active and showed a high level of cytotoxic potency, $IC_{50}\;51{\pm}2\;and\;15{\pm}2nM$ for 24 hand 48 h of incubation, respectively. The concentrations of digoxin, ouabain and proscillaridin A needed to inhibit [$^3H$]thymidine incorporation into DNA by 50% ($IC_{50}$) in MDA-MB-231 cells for 24 h of incubation were found to be $124{\pm}2nM,\;142{\pm}2nM,\;and\;48{\pm}2nM$, 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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Katarzyna Winnicka,Krzysztof Bielawski,Anna Bielawska,Wojciech Miltyk 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.10
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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Monika Lepiarczyk,Zbigniew Kału_za,Anna Bielawska,Robert Czarnomysy,Agnieszka Gornowicz,Krzysztof Bielawski 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.5
Evaluation of the cytotoxicity of novel octahydropyrazin[2,1-a:5,4-a0]diisoquinoline derivatives (1a–2c) employing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and inhibition of [3H]thymidineincorporation into DNA demonstrated that thesecompounds were more active than etoposide and camptothecinin both MDA-MB-231 and MCF-7 human breastcancer cells. Flow cytometric analysis after AnnexinV-FITC and propidium iodide staining also confirmed thatapoptosis was the main response of human breast cancercells to 1a–2c treatment. Our results suggest that apoptosisof human breast cancer cells in the presence of 1a–2cfollows the mitochondrial pathway, with the decrease inmitochondrial membrane potential and activation of caspase9, as well as by the external pathway with the significantincrease in caspase 8 expression. Cytotoxicproperties of compounds 1a–2c in cultured human breastcancer cells correlate to their ability to inhibit topoisomeraseI/II.
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