Dietary flavonoids and gene expression in human intestinal cells

Flavonoids represent a group of plant-derived dietary polyphenolic compounds. They were known to possess various biological activites.On tile molecular level, some flavonoids were known to affect the gene expression of soil bacteria, Rhizobiurn. The long-term goal of our study is to understand the role of dietary flavonoids on the expression of human genes. Here, we examined tile role of fiavonoids on the expression of metallothionein MT). MT was chosen as a model because its expression was known to be regulated and a substantial part of the promoter has l:)een cloned. The expression of MT in human intestinal Caco-2 cells was quantified by 109Cd-binding assay for the level of MT protein) and by Northern blots. One member of fiavonol, quercetin Q), was found to decrease basal MT expression dose-dependently. When included in the medium in the presence of 100 uM Zn, Q abolished the Zn-induced MT expression. Isofiavonoid, genistein G), on the other hand increased the basal expression of MT. In addition, the effect of G was synergistic to that of Zn. It is not clear through what mehanisms that Q and G affected MT expression. Previous study has shown that G was estrogenic but not Q using a reporter gene assay. Although estrogen-responsive element was not identified in the MT promoter, 17-estradiol also increased the expression of NIT. When G and 17JE were included simultaneously, there was no additive effect suggesting that the action of G and 17:E was mediated through the same mechanism. Antiestrogen, diethylstilbestrol, had no effect on the expression of MT by itself but decreased the 173E induced MT expression. Further studies of MT promoter is needed to determine the mechanism of flavonoid-gene interaction.