INDUCTION OF THE ANTICARCINOGENIC MARKER ENZYME, QUINONE REDUCTASE, IN MURINE HEPATOMA-CELLS IN-VITRO BY FLAVONOIDS

Some flavonoids induce phase II enzymes both in vivo and in vitro. We have determined the structural requirements for this activity by exami ning the ability of naturally-occurring flavonoids to induce the phase II enzyme, quinone reductase (NAD(P)H:quinone oxidoreductase; EC 1.6. 99.2), in murine Hepa1c1c7 cells. Hydroxylation of the B ring is not e ssential for induction, since galangin and kaempferol (with 0 and 1 hy droxyl in the B ring, respectively) are better inducers than quercetin (2 B ring hydroxyls). A 2,3 double bond in the C ring is essential fo r induction, since taxifolin, which has the same substitution pattern as quercetin but lacks the 2,3 double bond, is not an inducer. This is supported by catechin and epicatechin, which do not possess the 2,3 d ouble bond and are also not inducers. A S-hydroxyl group increases the activity but is not essential for induction, since apigenin is an ind ucer but kaempferol (which has the same structure as apigenin but poss esses a 3-hydroxyl group) is more effective. The data show that, of th e flavonoids, the flavonols are the most effective inducers of quinone reductase activity in Hepa1c1c7 cells (kaempferol similar to galangin > quercetin > myricetin-apigenin (a flavone)) and that flavanols and flavans are ineffective. (C) 1997 Elsevier Science Ireland Ltd.