title: Quercetin cumulatively enhances copper induction of metallothionein in intestinal cells.
abstract: Wilson's disease, a genetic copper-overload condition, is currently treated with zinc because of the ability of zinc to induce metallothionein. We are interested in nonmetal chemicals that may alter intestinal copper metabolism and thus help to alleviate copper toxicity. Previously, we have shown that quercetin, a dietary flavonoid, can chelate copper. This study further examined the interaction of quercetin and copper in intestinal epithelial cells. We found that quercetin enhanced metallothoinein induction by copper and the effect was dose dependent. Quercetin also exerted a cumulative effect after repeated exposure. Repeated low-dose treatment (3-10 microM) of cells with quercetin can lead to the same effect on metallothoinein as one higher concentration treatment (100 microM). This property of quercetin is distinct from its chemical interaction with copper, but both can contribute to a reduction of copper toxicity. Among other flavonoids tested, two other copper chelators, catechin and rutin, did not increase copper induction of metallothionein, whereas genistein, an isoflavone that does not interact with copper chemically, increased copper induction of metallothionein. The effect of quercetin on copper metabolism is unique. Quercetin decreased zinc-stimulated metallothionein expression and had no effect on the cadmium induction of metallothionein. The clinical application of our observation needs to be explored.
authors.affiliation: Department of Physical Therapy, State University of New York at Buffalo, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Kuo
authors.forename: C T
authors.initials: CT
authors.lastname: Huang
authors.forename: P
authors.initials: P
authors.lastname: Blum
authors.forename: C
authors.initials: C
authors.lastname: Chang
mesh_terms: D002104:Cadmium / Q000494:pharmacology; D002392:Catechin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012431:Rutin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D005419:Flavonoids; D012333:RNA, Messenger; D002104:Cadmium; D012431:Rutin; D003300:Copper; D002392:Catechin; D008668:Metallothionein; D011794:Quercetin; D019833:Genistein