Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 53, Issue 7, Pages 2489-2498Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf048524w
Keywords
human topoisomerase II; catalytic inhibitor; antitopoisomerase II activity; Vitis; grape cell culture; chemopreventive agents
Funding
- NCCIH NIH HHS [P50 AT-00477] Funding Source: Medline
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Grape and its cell culture extracts are rich in flavonoids and stilbenes that are biologically active. The objective of this study was to evaluate possible inhibitory effects of grape (a Vitis hybrid Bailey Alicant A) cell culture extract and subfractions on human DNA topoisomerase II catalytic activity and to characterize constituents in the most potent fractions. At 5 mu g/mL, grape cell crude extract and Toyopearl (TP) fractions 2-6 provided significantly greater inhibition of topoisomerase II catalytic activity than quercetin, a chemopreventive agent previously known as a topoisomerase catalytic inhibitor. The most potent topoisomerase II catalytic inhibitors from grape cell culture extracts in descending order of potency were TP fractions 4 and 6 (IC50 = 0.28-0.29 mu g/mL), TP-3 (IC50 = 0.74 mu g/mL), and crude extract (IC50 = 1.02 mu g/mL); each was significantly more potent than resveratrol (IC50 = 18.0 mu g/mL), another well-known chemopreventive topoisomerase II catalytic inhibitor. Using both high-performance liquid chromatography and liquid chromatography electrospray ionization mass spectrometry, constituents in TP-4 and TP-6 were characterized. These constituents included cyanidin-3,5-diglucoside, malvidin-3-acetylglucoside, peonidin-3-coumaryl-5-diglucoside, procyanidin B-1, procyanidin B-2, procyanidin B-5, procyanidin dimer digallate, procyanidin C-1, myricetin, and rutin, none of which have been previously characterized from grape cell cultures. The significant potency especially of TP-4 and TP-6 from grape cell cultures suggests that these fractions may have potential as chemopreventive agents.
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