Dietary flavonoids affect metallothionein (MT) expression in human intestinal cells

The expression of metal-binding protein, MT, was known to be affected by the trace mineral concentration. We examined the effect of dietary flavonoids, some were known to interact with metals, on the MT level (quantified by 109Cd-binding assay) in human intestinal cells, Caco2. Quercetin (Q) was found to interact with Cu (but not Zn) in isotonic buffer based on UV/Vis absorption spectrum analysis and when included in the cell culture medium at 100 iM for 48 hours, decreased baseline MT level to 59±107r. The inhibition by Q was time, dose-dependent and was observed for 100 fiM Zn-stimulated MT expression (26± 10% of control Zntreated cells) as well suggesting a physiologically-relevant interaction with metals. Isoflavonoid, genistein (G), did not show any interaction with metals in the buffer and was found to increase MT level when included in the cell culture medium in a time- and dose-dependent fashion. G at 100 μM increased MT level synergistically with 100μM Zn(0.057±0.016, 0.357±0.089, 0.541±0.220 and 2.067±0.408 μg MT/mg protein for control, G only, Zn only and Zn plus G, individually). The effect of G on MT level probably was not mediated through steroid-responsive element as MT level in intestinal cells was not sensitive to the dexamethasone treatment. More studies are needed to determine whether the changes in MT level were transcriptional events.