Purpose: Dietary flavonoids have been reported to be potent inhibitors of drug metabolizing enzymes. In the present study we examined the inducing effect of three of these compounds, chrysin, quercetin and genistein, on UDP-glucuronosyltransferase (UGT) in the human intestinal cell line Caco-2.
Methods: The induction of UGT by flavonoid pretreatment was studied both in the intact cells and cell homogenates, measured as the glucuronidation of chrysin, and by immunoblot analysis of the UGT 1A protein.
Results: Exposure of Caco-2 cells to 50 microM chrysin resulted in a 3.8-fold increase in chrysin glucuronidation in intact cells (p < 0.0001) with a 38% decrease in sulfation (p < 0.01). In the cell homogenate the induction was much larger, 14-fold. The induction was slow to develop with maximum induction after 3-4 days. Interestingly, the isoflavonoid genistein was without effect. Immunoblot analysis of Caco-2 cell microsomes with a UGT1A subfamily-selective antibody showed a markedly increased band at about 59 kDa, consistent with induction of one or more UGT1A isoforms. A 5-week exposure of Caco-2 cells to low concentrations (10 microM) of chrysin or quercetin also showed markedly increased glucuronidation activity.
Conclusions: Diet-mediated induction of intestinal UGT may be important for the bioavailability of carcinogens and other toxic chemicals as well as therapeutic drugs.