Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 71
Ferric citrate abolishes the induction of the hypoxia inducible factor HIF-1alpha
expression and restores the inhibition of cell proliferation produced by the flavonoid
quercetin
Anastasia Triantafyllou1, Panagiotis Liakos1, Andreas Tsakalof1, Georgia
Chachami1,2, Efrosyni Paraskeva2, Ilias Athanasiadis1, Paschalis-Adam Molyvdas2,
Eleni Georgatsou1, George Simos1 and Sophia Bonanou1
1Laboratory of Biochemistry and 2Laboratory of Physiology, Department of Medicine,
School of Health Sciences, University of Thessaly, Larissa, Greece.
E-mail: atsakal@med.uth.gr
Hypoxia induces the expression of the regulatory alpha subunit of the Hypoxia-Inducible
Factor-1 (HIF-1), by preventing its hydroxylation by O2 - and Fe2+-dependent prolyl
hydroxylases (PHDs), which target it for proteosomal degradation. Quercetin, a bioflavonoid
with anti-oxidant, metal-chelating, kinase-modulating and anti-proliferative properties, can
induce the expression of HIF-1alpha in normoxia, but its mechanism of action has not been
determined. In this study we characterized the induction of HIF-1alpha expression and
inhibition of proliferation in HeLa and ASM (airway smooth muscle) cells by quercetin and
examined the effect of iron on these processes. We also investigated the cellular uptake and
biotransformations of quercetin and its relevance for HIF-1alpha induction and growth
inhibition. Our data demonstrate that addition of excess Fe(III) can abrogate the quercetininduced
stabilization of HIF-1alpha in both cell systems. Moreover, the inhibition of DNA
synthesis, cell proliferation and cycle progression caused by quercetin can also be reversed by
excess iron. We propose that iron chelation is the key event in the induction of HIF-1alpha as
well as in the inhibition of cell proliferation produced by quercetin.
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