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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.