title: Topoisomerase II-targeting properties of a grapevine-shoot extract and resveratrol oligomers.
abstract: Grapevine-shoot extracts (GSE), containing trans-resveratrol and resveratrol oligomers, are commercially available as food supplements. Considering the topoisomerase-targeting properties of trans-resveratrol, the question of whether GSE affect these enzymes, thereby potentially causing DNA damage, was addressed. In a decatenation assay, GSE potently suppressed the catalytic activity of topoisomerase IIα (≥5 μg/mL). The resveratrol oligomers ε-viniferin, r2-viniferin, and hopeaphenol, isolated from GSE, were also identified as topoisomerase IIα inhibitors. In the in vivo complexes of enzyme to DNA (ICE) bioassay, neither GSE, r2-viniferin, nor hopeaphenol affected the level of enzyme-DNA intermediates in A431 cells, thus representing catalytic inhibitors rather than topoisomerase poisons. GSE caused moderate DNA strand breaks (≥25 μg/mL) in the comet assay. Taken together, GSE presumably acts as a catalytic inhibitor of topoisomerase II with r2-viniferin and hopeaphenol as potentially contributing constituents. However, the increase of FPG-sensitive sites points to an additional mechanism that may contribute to the DNA-damaging properties of GSE constituents.
authors.affiliation: Department of Food Chemistry and Toxicology, University of Vienna , Waehringerstrasse 38, A-1090 Vienna, Austria.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Baechler
authors.forename: Anika
authors.initials: A
authors.lastname: Schroeter
authors.forename: Martina
authors.initials: M
authors.lastname: Dicker
authors.forename: Pablo
authors.initials: P
authors.lastname: Steinberg
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D055162:Biocatalysis / Q000187:drug effects; D045744:Cell Line, Tumor; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology; D018520:Plant Shoots / Q000737:chemistry*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology; D027843:Vitis / Q000737:chemistry*
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D013267:Stilbenes; D004250:DNA Topoisomerases, Type II; D000077185:Resveratrol
keywords: DNA damage; grapevine-shoot extract; resveratrol oligomers; topoisomerase II