Biological Trace Element Research

, Volume 84, Issue 1–3, pp 1–10 | Cite as

Quercetin cumulatively enhances copper induction of metallothionein in intestinal cells

  • Shiu-Ming Kuo
  • Chin-Ting Huang
  • Penny Blum
  • Chawnshang Chang


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 µM) of cells with quercetin can lead to the same effect on metallothoinein as one higher concentration treatment (100 µM). 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.

Index Entries

Quercetin copper metallothionein cadmium genistein 


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Copyright information

© Humana Press Inc. 2001

Authors and Affiliations

  • Shiu-Ming Kuo
    • 1
    • 2
  • Chin-Ting Huang
    • 1
  • Penny Blum
    • 1
    • 3
  • Chawnshang Chang
    • 3
  1. 1.Nutrition Program, Department of Physical TherapyExercise and Nutrition SciencesUSA
  2. 2.Department of BiochemistryState University of New York at BuffaloBuffalo
  3. 3.George Whipple Laboratory for Cancer Research, Department of Pathology, Urology, and BiochemistryUniversity of RochesterRochester

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