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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
Catalytic inhibition of human DNA topoisomerase by phenolic compounds in Ardisia compressa extracts and their effect on human colon cancer cells.
Food and Chemical Toxicology 2006 August
Plant polyphenols, as those present in teas, have been associated with several health benefits. In this study, the main objectives were to identify and characterize the phenolic compounds in Ardisia compressa tea (AC) responsible for topoisomerase inhibition using a bioassay directed approach and modern analytical techniques, and to determine the cytotoxicity against human colon carcinoma cells. Inhibition of topoisomerase was determined by yeast and human topoisomerase biochemical assays. Identification and characterization of AC phenolic compounds were carried out using combined HPLC, MS and NMR techniques. Cytotoxicity studies were conducted using two human colorectal adenocarcinoma cell lines, HT-29 and Caco-2. LC-MS analysis of AC confirmed the presence of gallic acid, epicatechin gallate, several proanthocyanidin dimers, kaempferol, naringenin and ardisin derivatives. Topoisomerase II catalytic inhibitory activity of AC was due mainly to phenolic compounds extracted in the butanolic fraction (IC50: 1.33 microg/ml). Purification of this fraction resulted in the isolation of several compounds: peak 10 (IC50: 8.32 microg/ml), peaks 12/14 (IC75: 2.85 microg/ml) and peak 15 (IC50: 7.16 microg/ml). Characterization of peak 15, the most active fraction, led to the isolation of a naringenin isomer (C15H12O5), which had a significantly higher catalytic anti-topoisomerase II activity (IC50: 7.16 microg/ml) than commercial naringenin (IC50: 88.1 microg/ml). AC was cytotoxic to HT-29 (IC50: 57.9+/-11.6 microg/ml) and Caco-2 cells (IC50: 81.0+/-27.5 microg/ml). These findings provide basic information and suggest the potential use of active flavonoids in Ardisia compressa tea as chemopreventive agents.
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