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The flavonoid quercetin induces hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibits cell proliferation by depleting intracellular iron.
Free Radic Res. 2007 Mar; 41(3):342-56.FR

Abstract

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.

Authors+Show Affiliations

Laboratory of Biochemistry, Department of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17364964

Citation

Triantafyllou, Anastasia, et al. "The Flavonoid Quercetin Induces Hypoxia-inducible Factor-1alpha (HIF-1alpha) and Inhibits Cell Proliferation By Depleting Intracellular Iron." Free Radical Research, vol. 41, no. 3, 2007, pp. 342-56.
Triantafyllou A, Liakos P, Tsakalof A, et al. The flavonoid quercetin induces hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibits cell proliferation by depleting intracellular iron. Free Radic Res. 2007;41(3):342-56.
Triantafyllou, A., Liakos, P., Tsakalof, A., Chachami, G., Paraskeva, E., Molyvdas, P. A., Georgatsou, E., Simos, G., & Bonanou, S. (2007). The flavonoid quercetin induces hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibits cell proliferation by depleting intracellular iron. Free Radical Research, 41(3), 342-56.
Triantafyllou A, et al. The Flavonoid Quercetin Induces Hypoxia-inducible Factor-1alpha (HIF-1alpha) and Inhibits Cell Proliferation By Depleting Intracellular Iron. Free Radic Res. 2007;41(3):342-56. PubMed PMID: 17364964.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The flavonoid quercetin induces hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibits cell proliferation by depleting intracellular iron. AU - Triantafyllou,Anastasia, AU - Liakos,Panagiotis, AU - Tsakalof,Andreas, AU - Chachami,Georgia, AU - Paraskeva,Efrosyni, AU - Molyvdas,Pashalis-Adam, AU - Georgatsou,Elena, AU - Simos,George, AU - Bonanou,Sophia, PY - 2007/3/17/pubmed PY - 2007/5/24/medline PY - 2007/3/17/entrez SP - 342 EP - 56 JF - Free radical research JO - Free Radic Res VL - 41 IS - 3 N2 - 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. SN - 1071-5762 UR - https://www.unboundmedicine.com/medline/citation/17364964/The_flavonoid_quercetin_induces_hypoxia_inducible_factor_1alpha__HIF_1alpha__and_inhibits_cell_proliferation_by_depleting_intracellular_iron_ L2 - https://www.tandfonline.com/doi/full/10.1080/10715760601055324 DB - PRIME DP - Unbound Medicine ER -