Flavonoids induce HIF-1α but impair its nuclear accumulation and activity

Free Radical Biology and Medicine

Volumn 44, Issue 4, 2008, Pages 657-670

  Triantafyllou, Anastasia ^a   Mylonis, Ilias ^a   Simos, George ^a   Bonanou, Sophia ^a   Tsakalof, Andreas ^a  

^a School of Health Sciences   (Greece)

Author keywords

Cell signaling; Flavonoids; Free radicals; Hypoxia inducible factor 1; Iron; MAPK; Phosphorylation; Signal transduction; Structure activity relationship

Indexed keywords

BAICALEIN; DEFEROXAMINE; FISETIN; FLAVONOID; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IRON; IRON CHELATING AGENT; KAEMPFEROL; LUTEOLIN; QUERCETIN; RUTOSIDE; TAXIFOLIN;

ARTICLE; CELL NUCLEUS; CONTROLLED STUDY; DOWN REGULATION; FLUORESCENCE MICROSCOPY; HELA CELL; HUMAN; HUMAN CELL; HYPOXIA; IMMUNOFLUORESCENCE MICROSCOPY; IN VITRO STUDY; LIPOPHILICITY; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN INDUCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; TRANSCRIPTION REGULATION;

ACTIVE TRANSPORT, CELL NUCLEUS; CELL NUCLEUS; DEFEROXAMINE; FLAVONOIDS; HELA CELLS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IRON; MAP KINASE SIGNALING SYSTEM; PHOSPHORYLATION; TRANSCRIPTION, GENETIC;

EID: 38649134482     PISSN: 08915849     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2007.10.050     Document Type: Article

References (67)

1. Semenza G.L. HIF-1 and human disease: one highly involved factor. Genes Dev. 14 (2000) 1983-1991
2. Giaccia A., Siim B.G., and Johnson R.S. HIF-1 as a target for drug development. Nat. Rev. Drug Discovery 2 (2003) 803-811
3. Lee J.W., Bae S.H., Jeong J.W., Kim S.H., and Kim K.W. Hypoxia-inducible factor (HIF-1)alpha: its protein stability and biological functions. Exp. Mol. Med. 36 (2004) 1-12
4. Park J.W., Chun Y.S., and Kim M.S. Hypoxia-inducible factor 1-related diseases and prospective therapeutic tools. J. Pharmacol. Sci. 94 (2004) 221-232
5. Schofield C.J., and Ratcliffe P.J. Oxygen sensing by HIF hydroxylases. Nat. Rev., Mol. Cell Biol. 5 (2004) 343-354
6. 2-regulated gene expression. FASEB J. 16 (2002) 1151-1162
7. Semenza G.L. Targeting HIF-1 for cancer therapy. Nat. Rev., Cancer 3 (2003) 721-732
8. Greijer A.E., and van der Wall E. The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J. Clin. Pathol. 57 (2004) 1009-1014
9. Harris A.L. Hypoxia-a key regulatory factor in tumour growth. Nat. Rev., Cancer 2 (2002) 38-47
10. Chun Y.S., Kim M.S., and Park J.W. Oxygen-dependent and-independent regulation of HIF-1alpha. J. Korean Med. Sci. 17 (2002) 581-588
11. Chachami G., Simos G., Hatziefthimiou A., Bonanou S., Molyvdas P.A., and Paraskeva E. Cobalt induces hypoxia-inducible factor-1alpha expression in airway smooth muscle cells by a reactive oxygen species-and PI3K-dependent mechanism. Am. J. Respir. Cell Mol. Biol. 31 (2004) 544-551
12. Dery M.A., Michaud M.D., and Richard D.E. Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators. Int. J. Biochem. Cell Biol. 37 (2005) 535-540
13. Bardos J.I., and Ashcroft M. Negative and positive regulation of HIF-1: a complex network. Biochim. Biophys. Acta 1755 (2005) 107-120
14. Triantafyllou A., Liakos P., Tsakalof A., Georgatsou E., Simos G., and Bonanou S. Cobalt induces hypoxia-inducible factor-1alpha (HIF-1alpha) in HeLa cells by an iron-independent, but ROS-, PI-3K-and MAPK-dependent mechanism. Free Radic. Res. 40 (2006) 847-856
15. Chun Y.S., Yeo E.J., Choi E., Teng C.M., Bae J.M., Kim M.S., and Park J.W. Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells. Biochem. Pharmacol. 61 (2001) 947-954
16. Mabjeesh N.J., Post D.E., Willard M.T., Kaur B., Van Meir E.G., Simons J.W., and Zhong H. Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteasome pathway in prostate cancer cells. Cancer Res. 62 (2002) 2478-2482
17. Hasebe Y., Egawa K., Yamazaki Y., Kunimoto S., Hirai Y., Ida Y., and Nose K. Specific inhibition of hypoxia-inducible factor (HIF)-1 alpha activation and of vascular endothelial growth factor (VEGF) production by flavonoids. Biol. Pharm. Bull. 26 (2003) 1379-1383
18. Gong Y., and Agani F.H. Oligomycin inhibits HIF-1alpha expression in hypoxic tumor cells. Am. J. Physiol., Cell Physiol. 288 (2005) C1023-C1029
19. Vincent K.A., Feron O., and Kelly R.A. Harnessing the response to tissue hypoxia: HIF-1 alpha and therapeutic angiogenesis. Trends Cardiovasc. Med. 12 (2002) 362-367
20. Semenza G.L. Development of novel therapeutic strategies that target HIF-1. Expert Opin. Ther. Targets 10 (2006) 267-280
21. Hewitson K.S., McNeill L.A., and Schofield C.J. Modulating the hypoxia-inducible factor signaling pathway: applications from cardiovascular disease to cancer. Curr. Pharm. Des. 10 (2004) 821-833
22. Yeo E.J., Chun Y.S., and Park J.W. New anticancer strategies targeting HIF-1. Biochem. Pharmacol. 68 (2004) 1061-1069
23. Chau N.M., Rogers P., Aherne W., Carroll V., Collins I., McDonald E., Workman P., and Ashcroft M. Identification of novel small molecule inhibitors of hypoxia-inducible factor-1 that differentially block hypoxia-inducible factor-1 activity and hypoxia-inducible factor-1alpha induction in response to hypoxic stress and growth factors. Cancer Res. 65 (2005) 4918-4928
24. Losso J.N., and Bawadi H.A. Hypoxia inducible factor pathways as targets for functional foods. J. Agric. Food Chem. 53 (2005) 3751-3768
25. Middleton Jr. E., Kandaswami C., and Theoharides T.C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. Rev. 52 (2000) 673-751
26. Havsteen B.H. The biochemistry and medical significance of the flavonoids. Pharmacol. Ther. 96 (2002) 67-202
27. Scalbert A., Johnson I.T., and Saltmarsh M. Polyphenols: antioxidants and beyond. Am. J. Clin. Nutr. 81 (2005) 215S-217S
28. O'Prey J., Brown J., Fleming J., and Harrison P.R. Effects of dietary flavonoids on major signal transduction pathways in human epithelial cells. Biochem. Pharmacol. 66 (2003) 2075-2088
29. Williams R.J., Spencer J.P., and Rice-Evans C. Flavonoids: antioxidants or signalling molecules?. Free Radic. Biol. Med. 36 (2004) 838-849
30. Agullo G., Gamet-Payrastre L., Manenti S., Viala C., Remesy C., Chap H., and Payrastre B. Relationship between flavonoid structure and inhibition of phosphatidylinositol 3-kinase: a comparison with tyrosine kinase and protein kinase C inhibition. Biochem. Pharmacol. 53 (1997) 1649-1657
31. Wilson W.J., and Poellinger L. The dietary flavonoid quercetin modulates HIF-1 alpha activity in endothelial cells. Biochem. Biophys. Res. Commun. 293 (2002) 446-450
32. Welford R.W., Schlemminger I., McNeill L.A., Hewitson K.S., and Schofield C.J. The selectivity and inhibition of AlkB. J. Biol. Chem. 278 (2003) 10157-10161
33. Osada M., Imaoka S., and Funae Y. Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1alpha protein. FEBS Lett. 575 (2004) 59-63
34. Newcomb E.W., Ali M.A., Schnee T., Lan L., Lukyanov Y., Fowkes M., Miller D.C., and Zagzag D. Flavopiridol downregulates hypoxia-mediated hypoxia-inducible factor-1alpha expression in human glioma cells by a proteasome-independent pathway: implications for in vivo therapy. Neuro-oncology 7 (2005) 225-235
35. Grendys Jr. E.C., Blessing J.A., Burger R., and Hoffman J. A phase II evaluation of flavopiridol as second-line chemotherapy of endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol. Oncol. 98 (2005) 249-253
36. DeFeudis F.V., Papadopoulos V., and Drieu K. Ginkgo biloba extracts and cancer: a research area in its infancy. Fundam. Clin. Pharmacol. 17 (2003) 405-417
37. Pisters K.M., Newman R.A., Coldman B., Shin D.M., Khuri F.R., Hong W.K., Glisson B.S., and Lee J.S. Phase I trial of oral green tea extract in adult patients with solid tumors. J. Clin. Oncol. 19 (2001) 1830-1838
38. Laurie S.A., Miller V.A., Grant S.C., Kris M.G., and Ng K.K. Phase I study of green tea extract in patients with advanced lung cancer. Cancer Chemother. Pharmacol. 55 (2005) 33-38
39. Zhou Y.D., Kim Y.P., Li X.C., Baerson S.R., Agarwal A.K., Hodges T.W., Ferreira D., and Nagle D.G. Hypoxia-inducible factor-1 activation by (-)-epicatechin gallate: potential adverse effects of cancer chemoprevention with high-dose green tea extracts. J. Nat. Prod. 67 (2004) 2063-2069
40. Thomas R., and Kim M.H. Epigallocatechin gallate inhibits HIF-1alpha degradation in prostate cancer cells. Biochem. Biophys. Res. Commun. 334 (2005) 543-548
41. Galati G., and O'Brien P.J. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic. Biol. Med. 37 (2004) 287-303
42. Triantafyllou A., Liakos P., Tsakalof A., Chachami G., Paraskeva E., Molyvdas P.-A., Georgatsou E., Simos G., and Bonanou S. The flavonoid quercetin induces hypoxia-inducible factor-1α (HIF-1α) and inhibits cell proliferation by depleting intracellular iron. Free Radic. Res. 41 (2007) 342-356
43. Lyberopoulou A., Venieris E., Mylonis I., Chachami G., Pappas I., Simos G., Bonanou S., and Georgatsou E. MgcRacGAP interacts with HIF-1α and regulates its transcriptional activity. Cell Physiol. Biochem. 20 6 (2007) 995-1006
44. Chachami G., Paraskeva E., Georgatsou E., Bonanou S., and Simos G. Bacterially produced human HIF-1alpha is competent for heterodimerization and specific DNA-binding. Biochem. Biophys. Res. Commun. 331 (2005) 464-470
45. Spencer J.P., Abd-el-Mohsen M.M., and Rice-Evans C. Cellular uptake and metabolism of flavonoids and their metabolites: implications for their bioactivity. Arch. Biochem. Biophys. 423 (2004) 148-161
46. Hynes M.J., and O'Coinceanainn M. The kinetics and mechanisms of the reaction of iron(III) with gallic acid, gallic acid methyl ester and catechin. J. Inorg. Biochem. 85 (2001) 131-142
47. Engelmann M.D., Hutcheson R., and Cheng I.F. Stability of ferric complexes with 3-hydroxyflavone (flavonol), 5,7-dihydroxyflavone (chrysin), and 3′,4′-dihydroxyflavone. J. Agric. Food Chem. 53 (2005) 2953-2960
48. Schweigert N., Zehnder A.J., and Eggen R.I. Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals. Environ. Microbiol. 3 (2001) 81-91
49. Moridani M.Y., Siraki A., and O'Brien P.J. Quantitative structure toxicity relationships for phenols in isolated rat hepatocytes. Chem. Biol. Interact. 145 (2003) 213-223
50. Stenberg P., Bergstrom C.A., Luthman K., and Artursson P. Theoretical predictions of drug absorption in drug discovery and development. Clin. Pharmacokinet. 41 (2002) 877-899
51. Almasi J., Takacs-Novak K., Kokosi J., and Vamos J. Characterization of potential NMDA and cholecystokinin antagonists. II. Lipophilicity studies on 2-methyl-4-oxo-3H-quinazoline-3-alkyl-carboxylic acid derivatives. Int. J. Pharm. 180 (1999) 13-22
52. Dangles O., and Dufour C. Flavonoid-protein interactions. In: Andersen Q.M., and Markham K.R. (Eds). Flavonoids: chemistry, biochemistry and applications. 1st ed. (2006), Taylor & Francis, London 443-469
53. Esposito B.P., Epsztejn S., Breuer W., and Cabantchik Z.I. A review of fluorescence methods for assessing labile iron in cells and biological fluids. Anal. Biochem. 304 (2002) 1-18
54. Papanikolaou G., and Pantopoulos K. Iron metabolism and toxicity. Toxicol. Appl. Pharmacol. 202 (2005) 199-211
55. Vleugel M.M., Shvarts D., van der Wall E., and van Diest P.J. p300 and p53 levels determine activation of HIF-1 downstream targets in invasive breast cancer. Hum. Pathol. 37 (2006) 1085-1092
56. Martell, A.E., Smith, R.M., Motekaitis, R.S. NIST critical stability constants of metal complexes. NIST database, version 1.0, 1995.
57. Mylonis I., Chachami G., Samiotaki M., Panayotou G., Paraskeva E., Kalousi A., Georgatsou E., Bonanou S., and Simos G. Identification of MAPK phosphorylation sites and their role in the localization and activity of hypoxia-inducible factor-1alpha. J. Biol. Chem. 281 (2006) 33095-33106
58. Ma J., and Ptashne M. A new class of yeast transcriptional activators. Cell 51 (1987) 113-119
59. Hewitson K.S., McNeill L.A., Elkins J.M., and Schofield C.J. The role of iron and 2-oxoglutarate oxygenases in signalling. Biochem. Soc. Trans. 31 (2003) 510-515
60. 2 levels. J. Cell Sci. 116 (2003) 3041-3049
61. Mole D.R., Schlemminger I., McNeill L.A., Hewitson K.S., Pugh C.W., Ratcliffe P.J., and Schofield C.J. 2-Oxoglutarate analogue inhibitors of HIF prolyl hydroxylase. Bioorg. Med. Chem. Lett. 13 (2003) 2677-2680
62. Wang G.L., and Semenza G.L. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood 82 (1993) 3610-3615
63. Kietzmann T., and Gorlach A. Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin. Cell Dev. Biol. 16 (2005) 474-486
64. Galati G., Sabzevari O., Wilson J.X., and O'Brien P.J. Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics. Toxicology 177 (2002) 91-104
65. Spencer J.P.E., Rice-Evans C., and Williams R.J. Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. J. Biol. Chem. 278 (2003) 34783-34793
66. Moridani M.Y., Galati G., and O'Brien P.J. Comparative quantitative structure toxicity relationships for flavonoids evaluated in isolated rat hepatocytes and HeLa tumor cells. Chem. Biol. Interact. 139 (2002) 251-264
67. Moridani M.Y., Pourahmad J., Bui H., Siraki A., and O'Brien P.J. Dietary flavonoid iron complexes as cytoprotective superoxide radical scavengers. Free Radic. Biol. Med. 34 (2003) 243-253