Catalytic inhibition of human DNA topoisomerase II by interactions of grape cell culture polyphenols.
Previously, we isolated mixed polyphenolic fractions on a toyopearl matrix (TP-2 to TP-6) from grape cell cultures that were highly potent catalytic inhibitors in a human DNA topoisomerase II assay for cancer chemoprevention. The objectives of this study were to evaluate the potency of, and potential interactions between, individual fractions and some of the purified bioactive polyphenols that comprise these fractions on human DNA topoisomerase II catalytic activity. Treatments that combined anthocyanin-rich fractions (TP-2; 0.5 or 2.0 microg of dried material/mL), fractions containing catechins, procyanidin dimers, and flavanones (TP-4; 0.25 microg of dried material/mL), and/or fractions enriched with procyanidin oligomers and polymers (TP-6; 0.15 or 0.5 microg of dried material/mL) showed additive effects toward catalytic inhibition of the enzyme. Epicatechin gallate (IC50 = 0.029 microM), myricetin (0.39 microM), procyanidin B2 (PB2, 4.5 microM), and resveratrol (65.7 microM), constituents of the most bioactive mixed fraction from grape cell culture (TP-4), each individually provided potent catalytic inhibition of topoisomerase II. In addition, potentiating interactions between the PB2 and the other polyphenolic constituents mentioned above and between myricetin and resveratrol were clearly demonstrated. A synergistic interaction between myricetin and resveratrol was also confirmed with isobolographic analysis at a molar ratio of 1:70.
Department of Natural Resources and Environmental Sciences, University of Illinois at Urbana-Champaign, 1201 South Dorner Drive, Urbana, Illinois 61801, USA.
Jeong-Youn
JY
Jo
Elvira
E
Gonzalez de Mejia
Mary Ann
MA
Lila
D002384:Catalysis; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004347:Drug Interactions; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D059005:Topoisomerase II Inhibitors; D027843:Vitis / Q000737:chemistry*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II