Genistein increases metallothionein expression in human intestinal cells, Caco-2

Flavonoids found in common vegetables, fruits, and legumes have been shown to possess antioxidant property. This study is the first to demonstrate tha t one member of the flavonoid family, genistein, can induce the expression of metallothionein (a metal-binding protein with antioxidant property). We found the effect of genistein to be time- and dose-dependent (10-100 mu M). The effect can be observed at both protein and mRNA levels and was synergi stic to that of 30 mu M zinc. Genistein was shown previously to interact wi th the estrogen receptor and induce gene expression similar to estrogens at a lower affinity. We thus tested the hypothesis that the effect of geniste in on metallothionein expression was mediated through the steroid hormone p athway. We found that various glucocorticoids do not affect metallothionein expression in Caco-2 cells. 17 beta-estradiol at 10-100 mu M (concentratio ns much higher than needed to activate the estrogen response element) induc ed metallothionein expression in Caco-2 cells. However, a synthetic estroge n, diethylstilbestrol, did not increase metallothionein level at 10 mu M. 1 7 beta-Estradiol also did not act synergistically with zinc. Thus, genistei n may enhance metallothionein expression through an uncharacterized mechani sm. Further studies are needed to delineate the molecular mechanism and to determine whether the expression of other genes is also affected by geniste in.