Quercetin is a flavonol modifying numerous cell processes with potent antiproliferative effects on cancer cell-lines. The aim of this study was to explore by gene-array analysis the effect of quercetin on cancer-related gene expression in HepG2 cells, followed by verification with RT-PCR and analysis of the expected phenotypic changes (migration, cell cycle, cell proliferation). Quercetin induces significant changes on cell-adhesion related genes, leading to reduced migratory capacity and disorganization of the actin cytoskeleton. Several genes related to DNA functions, cellular metabolism and signal-transducer activities were also modified, while an early effect on Gprotein related cascades possibly via protease-activated receptor 2 and phospholipase C-1 was identified. Cyclin-D associated events in G1 and ubiquitin-dependent degradation of cyclin-D1 were also affected, resulting in cell-cycle arrest without activation of apoptosis pathways. In conclusion quercetin (3M) exerts its cellular effects by modifying numerous genes related to mechanisms involved in cancer initiation and promotion.
Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells.
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