Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells

Quercetin is a flavonol modifying a number of cell processes in different cell lines. Here, we present evidence that nonconjugated quercetin enters cells possibly via organic anion transporter polypeptides and quickly accumulates in the nucleus where it concentrates at distinct foci. Furthermore, it induces major transcriptional events with a high number of transcripts being modified over time and about 2200 transcripts being continuously influenced by the agent. The latter transcripts are related to cell cycle and adhesion, xenobiotic metabolism, immune-related factors and transcription. In addition, quercetin up-regulates the expression of estrogen receptors α and β. The overall outcome on cell fate is reflected by an inhibition of cell proliferation, cell cycle arrest in the G1 phase and reduction of the cellsʹ migratory potential due to actin cytoskeleton disorganization. Finally, we report that the flavonol modifies the transcription and/or activity of numerous transcription factors. In conclusion, our data support the idea that quercetin may actively accumulate in discrete cell structures and exert more than just antioxidant actions on epithelial cells by regulating mechanisms related to gene transcription.