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Original

The flavonoid quercetin induces hypoxia-inducible factor-1α (HIF-1α) and inhibits cell proliferation by depleting intracellular iron

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Pages 342-356 | Received 03 Jun 2006, Published online: 07 Jul 2009

References

  • Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 1999; 15: 551–578
  • Wenger RH. Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors and O2-regulated gene expression. FASEB J 2002; 16: 1151–1162
  • Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003; 3: 721–732
  • Wang GL, Jiang B-H, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 1995; 92: 5510–5514
  • Huang LE, Gu J, Schau M, Bunn HE. Regulation of hypoxia-inducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc Natl Acad Sci USA 1998; 95: 7987–7992
  • Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PW, Pugh CW, Ratcliffe PJ. Targetting of HIFα to the von Hippel Lindau ubiquitylation complex by O2-regulated hydroxylation. Science 2001; 292: 468–472
  • Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG, Jr. HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science 2001; 292: 464–468
  • Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O'Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dhanda A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 2001; 107: 43–54
  • Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick R. FIH-1 is an asparaginyl hydroxylase that regulates the transcriptional activity of hypoxia inducible factor. Genes Dev 2002; 16: 1466–1471
  • Kallio PJ, Okamoto K, O'Brien S, Carrero P, Makino Y, Tanaka H, Pollinger L. Signal transduction in hypoxic cells: Inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1-α. EMBO J 1998; 17: 6573–6586
  • Richard DE, Berra E, Gothie E, Roux D, Pouyssegur J. p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1α (HIF-1α) and enhance the transcriptional activity of HIF-1. J Biol Chem 1999; 274: 32631–32637
  • Semenza GL. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol 2002; 64: 993–998
  • Page EL, Robittaille GA, Pouyssegur J, Richard DE. Induction of hypoxia-inducible factor-1alpha by transcriptional and translational mechanisms. J Biol Chem 2002; 277: 48403–48409
  • Wang GL, Semenza GL. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA binding activity: Implications for models of hypoxia signal transduction. Blood 1993; 82: 3610–3615
  • Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 2004; 5: 343–354
  • Wilson WJ, Poellinger L. The dietary flavonoid quercetin modulates HIF-1 alpha activity in endothelial cells. Biochem Biophys Res Commun 2002; 293: 446–450
  • Hollman PC, Katan MB. Dietary flavonoids: Intake, health effects and bioavailability. Food Chem Toxicol 1999; 37: 937–942
  • Middleton EJr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease and cancer. Pharmacol Rev 2000; 52: 673–751
  • Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther 2002; 96: 67–202
  • Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 1995; 155: 381–386
  • Fotsis T, Pepper MS, Aktas E, Breit S, Rasku S, Adlercreutz H, Wahala K, Montesano R, Schweigerer L. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 1997; 57: 2916–2921
  • Rice-Evans C, Miller N, Paganga G. Structure–antioxidant activity relationships of flavonois and phenolic acids. Free Radic Biol Med 1996; 20: 933–956
  • Schweigert N, Zehnder AJB, Eggen RIL. Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals. Environ Microbiol 2001; 3: 81–91
  • Engelmann MD, Hutcheson R, Cheng IF. Stability of ferric complexes with 3-hydroxyflavone (flavonol), 5,7-dihydroxyflavone (chrysin), and 3′, 4′-dihydroxyflavone. J Agric Food Chem 2005; 53: 2953–2960
  • http://www.coldcure.com/html/stability_constants.html
  • Mira L, Fernandez MT, Santos M, Rocha R, Florencio MH, Jennings KR. Interaction of flavonoids with iron and copper ions: A mechanism for their antioxidant activity. Free Radic Res 2002; 36: 1199–1208
  • Melidou M, Riganakos K, Galaris D. Protection against nuclear DNA damage offered by flavonoids in cells exposed to hydrogen peroxide: The role of iron chelation. Free Radic Biol Med 2005; 39: 1591–1600
  • Chachami G, Simos G, Hatziefthymiou A, Bonanou S, Molyvdas PA, Paraskeva E. Cobalt induces hypoxia-inducible factor-1α expression in airway smooth muscle cells by a reactive oxygen species- and PI3K-dependent mechanism. Am J Respir Cell Mol Biol 2004; 31: 544–552
  • Devireddy LR, Gazin C, Zhu X, Green MR. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 2005; 123: 1293–1305
  • Spencer JP, Kuhnle GG, Williams RJ, Rice-Evans C. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem J 2003; 372: 173–181
  • Triantafyllou A, Liakos P, Tsakalof A, Georgatsou E, Simos G, Bonanou S. Cobalt induces hypoxia-inducible factor-1α (HIF-1α) in HeLa cells by an iron-independent, but ROS-, PI-3K- and MAPK-dependent mechanism. Free Radic Res 2006; 40: 847–856
  • Kawashini S, Oikawa S, Murata M. Evaluation for safety for antioxidant chemopreventive agents. Antioxid Redox Signal 2005; 7: 1728–1739
  • Kietzmann T, Gorlach A. Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin Cell Dev Biol 2005; 16: 474–486
  • Knowles HJ, Raval RR, Harris AL, Ratcliffe PJ. Effect of ascorbate on the activity of hypoxia-inducible factor 1α in cancer cells. Cancer Res 2003; 63: 1764–1768
  • Martell AE, Smith RM, Motekaitis RS. NIST critical stability constants of metal complexes. NIST data base. 1995
  • Herbert V, Shaw S, Jayatilleke E. Vitamin C-driven free radical generation from iron. J Nutr 1996; 126: 1213S–1220S
  • Kakhlon O, Cabantchik ZL. The labile iron pool: Characterization, measurement and participation in cellular processes. Free Radic Biol Med 2002; 33: 1037–1046
  • Papanikolaou G, Pantopoulos K. Iron metabolism and toxicity. Toxicol Appl Pharm 2005; 202: 199–211
  • Wang J, Buss JL, Chen G, Ponka P, Pantopoulos K. The prolyl 4-hydroxylase inhibitor ethyl-3,4-dihydrobenzoate generates effective iron deficiency in cultured cells. FEBS Lett 2002; 529: 309–312
  • Le NT, Richardson DR. The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim Biophys Acta 2002; 1603: 31–46
  • Templeton DL, Liu Y. Genetic regulation of cell function in response to iron overload or chelation. Biochim Biophys Acta 2003; 1619: 113–124
  • Hasebe Y, Egawa K, Yamazaki Y, Kunimoto S, Hirai Y, Ida Y, Nose K. Specific inhibition of hypoxia-inducible factor (HIF)-1a activation and of vascular endothelial growth factor (VEGF) production by flavonoids. Biol Pharm Bull 2003; 26: 1379–1383
  • Moon S-K, Cho G-O, Jung S-Y, Gal S-W, Kwon TK, Lee Y-C, Madamanchi NR, Kim C-H. Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: Role of ERK1/2, cell cycle regulation and matrix metalloproteinase-9. Biochem Biophys Res Comm 2003; 301: 1069–1078
  • Shih CM, Lin H, Liang YC, Lee WS, Bi WF, Juan SH. Concentration-dependent differential effects of quercetin on rat aortic smooth muscle cells. Eur J Pharmacol 2004; 496: 41–48
  • Elkins JM, Hewitson KS, McNeill LA, Seibel JF, Schlemminger I, Pugh CW, Ratcliffe PJ, Schofield CJ. Structure of factor-inhibiting hypoxia-inducible factor (FIH) reveals mechanism of oxidative modification of HIF-1α. J Biol Chem 2003; 278: 1802–1806
  • Welford RWD, Schlemminger I, McNeill LA, Hewitson KS, Schofield CJ. The selectivity of inhibition of AlkB. J Biol Chem 2003; 278: 10157–10161
  • Thomas R, Kim MH. Epigallocatechin gallate inhibits HIF-1α degradation in prostate cancer cells. Biochem Biophys Res Comm 2005; 334: 543–548
  • Zhou YD, Kim YP, Li XC, Baerson SR, Agarwal AK, Hodges TW, Ferreira D, Nagle DG. Hypoxia-inducible factor-1 activation by ( − )-epicatechin gallate: Potential adverse effects of cancer chemoprevention with high-dose green tea extracts. J Nat Prod 2004; 67: 2063–2069
  • Chen D, Daniel KG, Chen MS, Kuhn DJ, Landis-Piwowar KR, Dou QP. Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochem Parmacol 2005; 69: 1421–1432
  • Nose K. Inhibition by flavonoids of RNA synthesis in permeable WI-38 cells and of transcription by RNA polymerase II. Biochem Pharmacol 1984; 33: 3823–3827
  • Williams RJ, Spencer JPE, Rice-Evans C. Flavonoids: Antioxidants or signalling molecules?. Free Radic Biol Med 2004; 36: 838–849
  • Firuzi O, Lacanna A, Petrucci R, Marrosu G, Saso L. Evaluation of the antioxidant activity of flavonoids by “ferric reducing antioxidant power” assay and cyclic voltammetry. Biochim Biophys Acta 2005; 1721: 174–184
  • Hynes MJ, O'Coinceanainn M. Investigation of the release of iron from ferritin by naturally occurring antioxidants. J Inorg Biochem 2002; 90: 18–21
  • O'Prey J, Brown J, Fleming J, Harrison PR. Effects of dietary flavonoids on major signal transduction pathways in human epithelial cells. Biochem Pharmacol 2003; 66: 2075–2088
  • Guthie SJ, Johnson W, Dobson VL. The effect of dietary flavonoids on DNA damage (strand breaks and oxidized pyrimidines) and growth in human cells. Mutat Res 1997; 390: 141–151
  • Gupta K, Panda D. Perturbation of microtubule polymerization by quercetin through tubulin binding: A novel mechanism of its antiproliferative activity. Biochemistry 2002; 41: 13029–13038
  • Markaverich BM, Roberts RR, Alejandro MA, Johnson GA, Middleditch BS, Clark JH. Bioflavonoid interactions with rat uterine type II binding sites and growth inhibition. J Steroid Biochem 1988; 30: 71–78
  • Benhar M, Engelberg D, Levitzki A. ROS stress-activated kinases and stress signaling in cancer. EMBO Rep 2002; 3: 420–425

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