Catalytic inhibition of human DNA topoisomerase II by interactions of grape cell culture polyphenols

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Abstract

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 μg of dried material/mL), fractions containing catechins, procyanidin dimers, and flavanones (TP-4; 0.25 μg of dried material/mL), and/or fractions enriched with procyanidin oligomers and polymers (TP-6; 0.15 or 0.5 μg of dried material/mL) showed additive effects toward catalytic inhibition of the enzyme. Epicatechin gallate (IC50 = 0.029 μM), myricetin (0.39 μM), procyanidin B2 (PB2, 4.5 μM), and resveratrol (65.7 μM), 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.

Original languageEnglish (US)
Pages (from-to)2083-2087
Number of pages5
JournalJournal of Agricultural and Food Chemistry
Volume54
Issue number6
DOIs
StatePublished - Mar 22 2006

Keywords

  • Chemopreventive agents
  • Grape cell culture
  • Isobolographic analysis
  • Resveratrol
  • Synergistic interactions
  • Topoisomerase II catalytic inhibition
  • Vitis

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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