RESUMEN
Quercetin is a flavonoid that has roles in both cytoprotection and cytotoxicity. The relation of queretin's cytoprotective and cytotoxic effects are unknown. Quercetin has been shown to induce expression of hypoxia-inducible factor, a protein that is known to regulate transcription of the erythropoietin (EPO) gene, and EPO is known to have a cytoprotective effect. This study used HepG2 cells to assess whether the cell-protective and/or cytotoxic roles of quercetin are mediated by promotion of EPO production. Increases in the levels of HIF-1α protein and EPO mRNA were quercetin concentration-dependent, with significant increases observed from 10 µM quercetin. Silencing of EPO expression by si-EPO RNA attenuated quercetin-induced cytoprotection against hydrogen peroxide toxicity. Cytotoxicity, evidenced by the induction of apoptosis, was significantly increased by exposure to 50 µM quercetin. Specifically, the levels of cleaved caspase-3 and Bax and the rate of cell death increased, and the level of Bcl-2 decreased, in cells treated with 50 µM quercetin. In contrast, exposure to 10 µM quercetin attenuated cisplatin-induced apoptosis. However, quercetin's ability to protect cells from cisplatin-induced apoptosis was eliminated when EPO expression was silenced using si-EPO RNA. Together, these results suggested that quercetin's cytoprotective effects in HepG2 cells are mediated via EPO production.