Induction of UDP-Glucuronosyl-Transferase by the Flavonoids Chrysin and Quercetin in Caco-2 Cells

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Abstract
Purpose. Dietary flavonoids have been reported to be potent inhibitorsof drug metabolizing enzymes. In the present study we examined theinducing effect of three of these compounds, chrysin, quercetin andgenistein, on UDP-glucuronosyltransferase (UGT) in the humanintestinal cell line Caco-2. Methods. The induction of UGT by flavonoid pretreatment was studiedboth in the intact cells and cell homogenates, measured as theglucuronidation of chrysin, and by immunoblot analysis of the UGT 1A protein. Results. Exposure of Caco-2 cells to 50 μM chrysin resulted in a3.8-fold increase in chrysin glucuronidation in intact cells (p < 0.0001)with a 38% decrease in sulfation (p < 0.01). In the cell homogenatethe induction was much larger, 14-fold. The induction was slow todevelop with maximum induction after 3–4 days. Interestingly, theisoflavonoid genistein was without effect. Immunoblot analysis ofCaco-2 cell microsomes with a UGT1A subfamily-selective antibodyshowed a markedly increased band at about 59 kDa, consistent withinduction of one or more UGT1A isoforms. A 5-week exposure ofCaco-2 cells to low concentrations (10 μM) of chrysin or quercetinalso showed markedly increased glucuronidation activity. Conclusions. Diet-mediated induction of intestinal UGT may beimportant for the bioavailability of carcinogens and other toxicchemicals as well as therapeutic drugs.