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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in Caco-2 cells--potential role in carcinogen bioinactivation.

PURPOSE: Dietary flavonoids, present in fruits, vegetables and beverages have been demonstrated to be protective in cancer. Recently, we showed that the flavonoid chrysin induced UDP-glucuronosyltransferase ( UGT) activity and expression in the human intestinal cell line Caco-2. In the present study, we determined the specific UGT isoform(s) induced and whether this induction facilitates glucuronidation and potential detoxification of the colon carcinogen 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP). METHODS: The induction was studied by immunoblot analysis with UGT isoform-specific antibodies, by Northern blot analysis and using quercetin as an isoform-specific catalytic probe. Glucuronidation of N-hydroxy-PhIP was characterized using both recombinant UGTs and control and chrysin-treated microsomes. RESULTS: Western blot analysis showed that pretreatment of Caco-2 cells with 25 microM chrysin induced UGT1A1 without affecting the expression of UGTs 1A6, 1A9 and 2B7. Northern blot analysis showed markedly increased expression of UGT1AI mRNA after chrysin treatment. Similarly, glucuronidation of quercetin was greatly increased in a UGT1A1-specific way. The induction of UGT1A1 in the Caco-2 cells resulted in a 10-fold increase in the glucuronidation of N-hydroxy-PhIP. CONCLUSION: Dietary flavonoid-mediated induction of intestinal UGT1A1 may be important for the glucuronidation and detoxification of colon and other carcinogens as well as for the presystemic metabolism of therapeutic drugs.[1]

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