INTERACTION OF THE FLAVONOID QUERCETIN WITH ZINC CATIONS MODULATES ZINC HOMEOSTASIS AND ZINC SIGNALLING IN HEPATOCARCINOMA CELLS IN VITRO

DABBAGH-BAZARBACHI, H.; QUESADA, I.; BUSTOS, M.; AROLA, L.; FERNANDEZ-LARREA, J.

Reus, Tarragona

Congreso; World Forum for Nutrition Research: Mediterranean Food and Health and Disease; 2013

Background and objectives. Zinc, the second most abundant transition metal in humans, is an essential micronutrient with structural, catalytic and signaling function and shows antioxidant action in cells. Quercetin is one of the most abundant polyphenols found in fruits and vegetables distinctive of the Mediterranean Diet; its consumption is beneficial for prevention of chronic diseases such as obesity, hypertension, diabetes, Alzheimer or cancer. Food polyphenols are known to act as antioxidants and as signaling molecules, and to form complexes with copper and iron thereby affecting their bioavailability. In this work, we seek to check whether quercetin interacts with zinc and to evaluate the effect of this interaction on intracellular zinc homeostasis and zinc signaling in an in vitro model of hepatic tumor cells.Methods and results. Quercetin strongly binds to zinc cations in solution as shown by the quenching of zincdependent Zinquin fluorescence. Administration of quercetin together with supplemental zinc to hepatocarcinoma cells results in enhanced expression of the zinc-store protein metallothionein and the zinc-export transporter ZnT1 (as determined by RT-PCR); total intracellular zinc content (assayed by FAAS) and cytoplasmic labile zinc (monitored by Zinquin fluorescence) are increased. Western-blot analyses show that low doses of quercetin greatlyenhance zinc-induced phosphorylation of Akt and, vice versa, low doses of zinc enhance the phosphorylation of Akt induced by quercetin. Appropriate combinations of zinc and quercetin result in morphological changes characteristics of apoptotic processes, as revealed by propidium iodide staining.Conclusions. These results show that combinations of zinc with quercetin are more effective that the single compounds in modulating intracellular zinc homeostasis and signaling. They also suggest that polyphenols may act as zinc ionophores. Polyphenol-zinc complexes may be useful for controlling multiple cellular processes such as apoptosis.