Topoisomerase II-targeting properties of a grapevine-shoot extract and resveratrol oligomers.

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.