Free Radic Res. 2007 Mar ;41 (3):342-56 17364964
The flavonoid quercetin induces hypoxia-inducible factor-1alpha
(HIF-1alpha) and inhibits cell proliferation by depleting
intracellular iron.
[My paper] Anastasia Triantafyllou , Panagiotis Liakos , Andreas
Tsakalof , Georgia Chachami , Efrosyni Paraskeva , Pashalis-Adam
Molyvdas , Elena Georgatsou , George Simos , Sophia Bonanou
Quercetin, a flavonoid with anti-oxidant, metal chelating, kinase
modulating and anti-proliferative properties, can induce hypoxia-
inducible factor-1alpha (HIF-1alpha) in normoxia, but its mechanism of
action has not been determined. In this study we characterized the
induction of HIF-1alpha and the inhibition of cell proliferation
caused by quercetin in HeLa and ASM (airway smooth muscle) cells and
examined the effect of iron on these processes. Furthermore, we
investigated the relevance of the intracellular levels of quercetin to
HIF-1alpha expression and cell proliferation. Our data demonstrate
that quercetin depletes intracellular calcein-chelatable iron and that
supplying additional iron from extracellular or intracellular pools
abrogates the induction of HIF-1alpha by quercetin. Moreover, addition
of iron reverses the quercetin-induced inhibition of DNA synthesis,
cell proliferation and cycle progression, but to different extents,
depending on cell type. We propose that quercetin stabilises
HIF-1alpha and inhibits cell proliferation predominantly by decreasing
the concentration of intracellular iron through chelation.
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