Natural toxicants in the food supply: In vitro investigation of the potential mechanism of action of the dietary flavonoid quercetin

Abstract

Quercetin, a natural flavonoid, is a well-known genotoxin, but its carcinogenicity is unclear. The objective of these studies was to investigate and compare the effects on glycolytic flux of quercetin and the known toxic xenobiotic phorbol 12-myristate 13-acetate (PMA) in a cell culture model. Rat kidney cells (NRK-49F) grown in culture were exposed to either quercetin (29 nM) or PMA (16 nM) in a dimethyl sulphoxide carrier. PMA treatment led to the expected increase in fructose-2,6-bisphosphate (Fru-2,6-P₂) compared to the control value after a 6h incubation. In addition, there was an increase in the metabolite after the addition of quercetin. Lactate release increased after exposure to PMA and after exposure to quercetin. No significant additivity of the effects of PMA together with quercetin was observed. It was found that the activity of phosphofructo-kinase-2 (PFK-2), the enzyme that catalyses the synthesis of Fru-2,6-P₂, was increased after exposure to PMA and after exposure to quercetin. The increase in Fru-2,6-P₂ and PFK-2 brought about by these two agents was prevented when the cells were incubated in the presence of cycloheximide (1 mM). The overall findings suggest that quercetin stimulates glycolysis in a similar fashion to PMA.