Iron chelator-mediated alterations in gene expression: Identification of novel iron-regulated molecules that are molecular targets of hypoxia-inducible factor-1α and p53

Molecular Pharmacology

Volumn 77, Issue 3, 2010, Pages 443-458

  Saletta, Federica ^a   Rahmanto, Yohan Suryo ^a   Noulsri, Egarit ^b   Richardson, Des R ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b MAHIDOL UNIVERSITY   (Thailand)

Author keywords

[No Author keywords available]

Indexed keywords

2 HYDROXY 1 NAPHTHYLALDEHYDE ISONICOTINOYL HYDRAZONE; AMYLOID PRECURSOR PROTEIN; CHELATING AGENT; COMPLEMENTARY DNA; COMPLEMENTARY RNA; DEFEROXAMINE; EARLY GROWTH RESPONSE FACTOR 1; GROWTH DIFFERENTIATION FACTOR 15; HYDRAZONE DERIVATIVE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IRON; LIGAND; MESSENGER RNA; PROTEIN P53; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL STRAIN MCF 7; CHEMICAL STRUCTURE; CONTROLLED STUDY; GENE EXPRESSION REGULATION; GENOME; HUMAN; HUMAN CELL; IRON CHELATION; IRON DEFICIENCY; MICROARRAY ANALYSIS; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR CELL; WESTERN BLOTTING;

ANIMALS; APOPTOSIS; CELL PROLIFERATION; CELLS, CULTURED; GENE EXPRESSION REGULATION; GENE TARGETING; GENES, P53; GROWTH INHIBITORS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IRON; IRON CHELATING AGENTS; IRON-REGULATORY PROTEINS; MICE; MICE, KNOCKOUT; TUMOR CELLS, CULTURED;

EID: 77149125234     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.109.061028     Document Type: Article

References (67)

1. An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, and Neckers LM (1998) Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature 392:405-408.
2. Bai L and Merchant JL (2007) A role for CITED2, a CBP/p300 interacting protein, in colon cancer cell invasion. FEBS Lett 581:5904-5910.
3. Baron V, Adamson ED, Calogero A, Ragona G, and Mercola D (2006) The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53, and fibronectin. Cancer Gene Ther 13:115-124.
4. Bianchi L, Tacchini L, and Cairo G (1999) HIF-1-mediated activation of transferrin receptor gene transcription by iron chelation. Nucleic Acids Res 27:4223-4227.
5. Bruick RK (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci U S A 97:9082-9087.
6. Buss JL, Torti FM, and Torti SV (2003) The role of iron chelation in cancer therapy. Curr Med Chem 10:1021-1034.
7. Chakrabarti J, Turley H, Campo L, Han C, Harris AL, Gatter KC, and Fox SB (2004) The transcription factor DEC1 (stra13, SHARP2) is associated with the hypoxic response and high tumour grade in human breast cancers. Br J Cancer 91:954-958.
8. Chaston TB, Lovejoy DB, Watts RN, and Richardson DR (2003) Examination of the antiproliferative activity of iron chelators: multiple cellular targets and the different mechanism of action of triapine compared with desferrioxamine and the potent pyridoxal isonicotinoyl hydrazone analogue 311. Clin Cancer Res 9:402-414.
9. Choi BH, Kim CG, Bae YS, Lim Y, Lee YH, and Shin SY (2008) p21 Waf1/Cip1 expression by curcumin in U-87MG human glioma cells: role of early growth response-1 expression. Cancer Res 68:1369-1377.
10. Currie MJ, Hanrahan V, Gunningham SP, Morrin HR, Frampton C, Han C, Robinson BA, and Fox SB (2004) Expression of vascular endothelial growth factor D is associated with hypoxia inducible factor (HIF-1alpha) and the HIF-1alpha target gene DEC1, but not lymph node metastasis in primary human breast carcinomas. J Clin Pathol 57:829-834.
11. Darnell G and Richardson DR (1999) The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents III: the effect of the ligands on molecular targets involved in proliferation. Blood 94:781-792.
12. Dayan F, Roux D, Brahimi-Horn MC, Pouyssegur J, and Mazure NM (2006) The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxiainducible factor-1alpha. Cancer Res 66:3688-3698.
13. Denko N, Schindler C, Koong A, Laderoute K, Green C, and Giaccia A (2000) Epigenetic regulation of gene expression in cervical cancer cells by the tumor microenvironment. Clin Cancer Res 6:480-487.
14. el-Deiry WS, Kern SE, Pietenpol JA, Kinzler KW, and Vogelstein B (1992) Definition of a consensus binding site for p53. Nat Genet 1:45-49.
15. Elstner A, Holtkamp N, and von Deimling A (2007) Involvement of Hif-1 in desferrioxamine-induced invasion of glioblastoma cells. Clin Exp Metastasis 24:57-66.
16. Fei P, Wang W, Kim SH, Wang S, Burns TF, Sax JK, Buzzai M, Dicker DT, McKenna WG, Bernhard EJ, and El-Deiry WS (2004) Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growth. Cancer Cell 6:597-609.
17. Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, and Eck MJ (2003) Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2. Nat Struct Biol 10:504-512.
18. Gao J and Richardson DR (2001) The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents, IV: The mechanisms involved in inhibiting cell-cycle progression. Blood 98:842-850.
19. Gess B, Hofbauer KH, Wenger RH, Lohaus C, Meyer HE, and Kurtz A (2003) The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-Lalpha. Eur J Biochem 270:2228-2235.
20. Guo K, Searfoss G, Krolikowski D, Pagnoni M, Franks C, Clark K, Yu KT, Jaye M, and Ivashchenko Y (2001) Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ 8:367-376.
21. Ivanova AV, Ivanov SV, Danilkovitch-Miagkova A, and Lerman MI (2001) Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway. J Biol Chem 276:15306-15315.
22. Jutooru I, Chadalapaka G, Chintharlapalli S, Papineni S, and Safe S (2009) Induction of apoptosis and nonsteroidal anti-inflammatory drug-activated gene 1 in pancreatic cancer cells by a glycyrrhetinic acid derivative. Mol Carcinog 48:692-702.
23. Lakhal S, Talbot NP, Crosby A, Stoepker C, Townsend AR, Robbins PA, Pugh CW, Ratcliffe PJ, and Mole DR (2009) Regulation of growth differentiation factor 15 expression by intracellular iron. Blood 113:1555-1563.
24. Le NT and Richardson DR (2004) Iron chelators with high antiproliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: a link between iron metabolism and proliferation. Blood 104:2967-2975.
25. Lee H and Paik SG (2006) Regulation of BNIP3 in normal and cancer cells. Mol Cells 21:1-6.
26. Liang SX and Richardson DR (2003) The effect of potent iron chelators on the regulation of p53: examination of the expression, localization and DNA-binding activity of p53 and the transactivation of WAF1. Carcinogenesis 24:1601-1614.
27. Liu J, Grogan L, Nau MM, Allegra CJ, Chu E, and Wright JJ (2001) Physical interaction between p53 and primary response gene Egr-1. Int J Oncol 18:863-870.
28. Liu Y, Cox SR, Morita T, and Kourembanas S (1995) Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5′ enhancer. Circ Res 77:638-643.
29. Lu X, Bocangel D, Nannenga B, Yamaguchi H, Appella E, and Donehower LA (2004) The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. Mol Cell 15:621-634.
30. Lu X, Ma O, Nguyen TA, Jones SN, Oren M, and Donehower LA (2007) The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop. Cancer Cell 12:342-354.
31. Lu X, Nannenga B, and Donehower LA (2005) PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev 19:1162-1174.
32. Martinez JM, Sali T, Okazaki R, Anna C, Hollingshead M, Hose C, Monks A, Walker NJ, Baek SJ, and Eling TE (2006) Drug-induced expression of nonsteroidal antiinflammatory drug-activated gene/macrophage inhibitory cytokine-1/ prostatederived factor, a putative tumor suppressor, inhibits tumor growth. J Pharmacol Exp Ther 318:899-906.
33. May D, Itin A, Gal O, Kalinski H, Feinstein E, and Keshet E (2005) Ero1-L alpha plays a key role in a HIF-1-mediated pathway to improve disulfide bond formation and VEGF secretion under hypoxia: implication for cancer. Oncogene 24:1011-1020.
34. Miyazaki K, Kawamoto T, Tanimoto K, Nishiyama M, Honda H, and Kato Y (2002) Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes. J Biol Chem 277:47014-47021.
35. Morrish DW, Dakour J, and Li H (2001) Life and death in the placenta: new peptides and genes regulating human syncytiotrophoblast and extravillous cytotrophoblast lineage formation and renewal. Curr Protein Pept Sci 2:245-259.
36. Muckenthaler M, Richter A, Gunkel N, Riedel D, Polycarpou-Schwarz M, Hentze S, Falkenhahn M, Stremmel W, Ansorge W, and Hentze MW (2003) Relationships and distinctions in iron-regulatory networks responding to interrelated signals. Blood 101:3690-3698.
37. Ozaki T, Li Y, Kikuchi H, Tomita T, Iwatsubo T, and Nakagawara A (2006) The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis. Biochem Biophys Res Commun 351:57-63.
38. Packer LM, Pavey SJ, Boyle GM, Stark MS, Ayub AL, Rizos H, and Hayward NK (2007) Gene expression profiling in melanoma identifies novel downstream effectors of p14ARF. Int J Cancer 121:784-790.
39. Richardson D, Ponka P, and Baker E (1994) The effect of the iron(III) chelator, desferrioxamine, on iron and transferrin uptake by the human malignant melanoma cell. Cancer Res 54:685-689.
40. Richardson DR and Bernhardt PV (1999) Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with antitumour activity. J Biol Inorg Chem 4:266-273.
41. Richardson DR, Tran EH, and Ponka P (1995) The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents. Blood 86:4295-4306.
42. Rogers JT, Randall JD, Cahill CM, Eder PS, Huang X, Gunshin H, Leiter L, McPhee J, Sarang SS, Utsuki T, Greig NH, Lahiri DK, Tanzi RE, Bush AI, Giordano T, and Gullans SR (2002) An iron-responsive element type II in the 5′-untranslated region of the Alzheimer's amyloid precursor protein transcript. J Biol Chem 277:45518-45528.
43. Rong Y, Hu F, Huang R, Mackman N, Horowitz JM, Jensen RL, Durden DL, Van Meir EG, and Brat DJ (2006) Early growth response gene-1 regulates hypoxiainduced expression of tissue factor in glioblastoma multiforme through hypoxiainducible factor-1-independent mechanisms. Cancer Res 66:7067-7074.
44. Saarikoski ST, Rivera SP, and Hankinson O (2002) Mitogen-inducible gene 6 (MIG-6), adipophilin and tuftelin are inducible by hypoxia. FEBS Lett 530:186-190.
45. Sanchez M, Galy B, Muckenthaler MU, and Hentze MW (2007) Iron-regulatory proteins limit hypoxia-inducible factor-2alpha expression in iron deficiency. Nat Struct Mol Biol 14:420-426.
46. Secchiero P, Barbarotto E, Tiribelli M, Zerbinati C, di Iasio MG, Gonelli A, Cavazzini F, Campioni D, Fanin R, Cuneo A, and Zauli G (2006) Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood 107:4122-4129.
47. Semenza GL (1999) Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 15:551-578.
48. Sevier CS and Kaiser CA (2008) Ero1 and redox homeostasis in the endoplasmic reticulum. Biochim Biophys Acta 1783:549-556.
49. Sperandio S, Fortin J, Sasik R, Robitaille L, Corbeil J, and de Belle I (2009) The transcription factor Egr1 regulates the HIF-1alpha gene during hypoxia. Mol Carcinog 48:38-44.
50. Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson RS, 2nd, Wang M, and Liang P. NDRG1 is necessary for p53-dependent apoptosis. J Biol Chem 279(47):48930-48940, 2004.
51. Suryo Rahmanto Y, Dunn LL, and Richardson DR (2007) Identification of distinct changes in gene expression after modulation of melanoma tumor antigen p97 (melanotransferrin) in multiple models in vitro and in vivo. Carcinogenesis 28:2172-2183.
52. Tai TC, Wong-Faull DC, Claycomb R, and Wong DL (2009) Hypoxic stress-induced changes in adrenergic function: role of HIF1 alpha. J Neurochem 109:513-524.
53. Takayama K, Tsutsumi S, Suzuki T, Horie-Inoue K, Ikeda K, Kaneshiro K, Fujimura T, Kumagai J, Urano T, Sakaki Y, Shirahige K, Sasano H, Takahashi S, Kitamura T, Ouchi Y, Aburatani H, and Inoue S (2009) Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth. Cancer Res 69:137-142.
54. Togashi A, Katagiri T, Ashida S, Fujioka T, Maruyama O, Wakumoto Y, Sakamoto Y, Fujime M, Kawachi Y, Shuin T, and Nakamura Y (2005) Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marker for renal cell carcinoma and potential target for molecular therapy. Cancer Res 65:4817-4826.
55. van den Beucken T, Magagnin MG, Savelkouls K, Lambin P, Koritzinsky M, and Wouters BG (2007) Regulation of Cited2 expression provides a functional link between translational and transcriptional responses during hypoxia. Radiother Oncol 83:346-352.
56. Wang R, Zhang YW, Zhang X, Liu R, Zhang X, Hong S, Xia K, Xia J, Zhang Z, and Xu H (2006) Transcriptional regulation of APH-1A and increased gammasecretase cleavage of APP and Notch by HIF-1 and hypoxia. FASEB J 20:1275-1277.
57. Whitnall M, Howard J, Ponka P, and Richardson DR (2006) A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proc Natl Acad Sci U S A 103:14901-14906.
58. Yamada K and Miyamoto K (2005) Basic helix-loop-helix transcription factors, BHLHB2 and BHLHB3; their gene expressions are regulated by multiple extracellular stimuli. Front Biosci 10:3151-3171.
59. Yan SF, Lu J, Zou YS, Soh-Won J, Cohen DM, Buttrick PM, Cooper DR, Steinberg SF, Mackman N, Pinsky DJ, and Stern DM (1999) Hypoxia-associated induction of early growth response-1 gene expression. J Biol Chem 274:15030-15040.
60. Yang G, Zhang G, Pittelkow MR, Ramoni M, and Tsao H (2006) Expression profiling of UVB response in melanocytes identifies a set of p53-target genes. J Invest Dermatol 126:2490-2506.
61. Yoshioka H, Kamitani H, Watanabe T, and Eling TE (2008) Nonsteroidal antiinflammatory drug-activated gene (NAG-1/GDF15) expression is increased by the histone deacetylase inhibitor trichostatin A. J Biol Chem 283:33129-33137.
62. Yu Y, Kalinowski DS, Kovacevic Z, Siafakas AR, Jansson PJ, Stefani C, Lovejoy DB, Sharpe PC, Bernhardt PV, and Richardson DR (2009) Thiosemicarbazones from the old to new: iron chelators that are more than just ribonucleotide reductase inhibitors. J Med Chem 52:5271-5294.
63. Yuan J, Lovejoy DB, and Richardson DR (2004) Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment. Blood 104:1450-1458.
64. Zagurovskaya M, Shareef MM, Das A, Reeves A, Gupta S, Sudol M, Bedford MT, Prichard J, Mohiuddin M, and Ahmed MM (2009) EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells. Oncogene 28:1121-1131.
65. Zhang F, Wang W, Tsuji Y, Torti SV, and Torti FM (2008) Post-transcriptional modulation of iron homeostasis during p53-dependent growth arrest. J Biol Chem 283:33911-33918.
66. Zhang X, Zhou K, Wang R, Cui J, Lipton SA, Liao FF, Xu H, and Zhang YW (2007) Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 282:10873-10880.
67. Zhou D, Chen B, Ye JJ, and Chen S (2004) A novel crosstalk mechanism between nuclear receptor-mediated and growth factor/Ras-mediated pathways through PNRC-Grb2 interaction. Oncogene 23:5394-5404.