Human DNA topoisomerase inhibitors from Potentilla argentea and their cytotoxic effect against MCF-7.
Two polyphenolics, kaempferol 3-O-beta-D-(6"-E-p-coumaroyl)-glucopyranoside (tiliroside) (1) and methyl brevifolincarboxylate (2) isolated from aerial parts of Potentilla argentea L. (Rosaceae) were evaluated for their cytotoxicities against human breast carcionoma cell line (MCF-7) and their DNA-binding ability. The DNA-binding ability of these compounds was studied by means of the human DNA topoisomerase I and II inhibition assay and ethidium displacement assay using calf thymus DNA, poly(dA-dT)2 and poly(dG-dC)2. Compound 2 was much more active and showed a higher level of cytotoxic potency than compound 1, with IC50 values of 1.11 +/- 2 microM and 21.60 +/- 2 microM, respectively. In DNA topoisomerase I and II inhibition in vitro assays both investigated compounds 1 and 2 were more effective against topoisomerase II than I. The results of DNA binding studies reveal that methyl brevifolincarboxylate had a greater DNA binding affinity that tiliroside, which correlates with its greater potency as a topoisomerase I/II inhibitor.
Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Białystok, Poland. tomczyk@amb.edu.pl
M
M
Tomczyk
D
D
Drozdowska
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A
Bielawska
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K
Bielawski
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J
Gudej
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004996:Ethidium / Q000737:chemistry; D005260:Female; D005419:Flavonoids; D006801:Humans; D009336:Necrosis; D011068:Poly G / Q000737:chemistry; D011067:Poly dA-dT / Q000737:chemistry; D031987:Potentilla / Q000737:chemistry*; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D005419:Flavonoids; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C052083:tiliroside; D011068:Poly G; D011067:Poly dA-dT; D004247:DNA; D004996:Ethidium; D002166:Camptothecin