title: Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells.
abstract: 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 cells' 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.
authors.affiliation: Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.forename: Artemisia-Phoebe
authors.initials: AP
authors.lastname: Nifli
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pelekanou
authors.forename: Vasileia-Ismini
authors.initials: VI
authors.lastname: Alexaki
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Theodoropoulos
authors.forename: Joseph
authors.initials: J
authors.lastname: Vercauteren
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D011794:Quercetin / Q000494:pharmacology*; D014157:Transcription Factors; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D047628:Estrogen Receptor alpha; D014157:Transcription Factors; D011794:Quercetin