Tuning cell cycle regulation with an iron key

Cell Cycle

Volumn 6, Issue 16, 2007, Pages 1982-1994

  Yu, Yu ^a   Kovacevic, Zaklina ^a   Richardson, Des R ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Cell cycle; Cyclin D1; Iron; Iron chelators; p21CIP1 WAF1; p53

Indexed keywords

2 HYDROXY 1 NAPTHYLALDEHYDE ISONICOTINOYL HYDRAZONE; 3 AMINOPICOLINALDEHYDE THIOSEMICARBAZONE; 311; ANTINEOPLASTIC AGENT; CYCLIN D1; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLIN DEPENDENT KINASE INHIBITOR 1B; DEFEROXAMINE; HEPCIDIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IRON CHELATING AGENT; IRON REGULATORY PROTEIN 1; IRON REGULATORY PROTEIN 2; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE P38; O TRENSOX; PROTEIN P53; RIBONUCLEOTIDE REDUCTASE; TACHPYRIDINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL CYCLE REGULATION; CELL CYCLE S PHASE; CELL METABOLISM; CELL PROLIFERATION; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DNA SYNTHESIS; DOWN REGULATION; DRUG MECHANISM; ENZYME DEGRADATION; ENZYME REGULATION; HUMAN; IRON DEPLETION; IRON METABOLISM; IRON STORAGE; IRON TRANSPORT; LEUKEMIA; MONOTHERAPY; NONHUMAN; PROTEIN EXPRESSION; REVIEW; UPREGULATION;

EID: 34548286520     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.6.16.4603     Document Type: Review

References (212)

1. Hershko C. Control of disease by selective iron depletion: A novel therapeutic strategy utilizing iron chelators. Baillieres Clin Haematol 1994; 7:965-1000.
2. Buss JL, Greene BT, Turner J, Torti FM, Torti SV. Iron chelators in cancer chemotherapy. Curr Top Med Chem 2004; 4:1623-35.
3. Andrews NC. Disorders of iron metabolism. N Engl J Med 1999; 341:1986-95.
4. Thelander L, Graslund A, Thelander M. Continual presence of oxygen and iron required for mammalian ribonucleotide reduction: Possible regulation mechanism. Biochem Biophys Res Commun 1983; 110:859-65.
5. Nyholm S, Mann GJ, Johansson AG, Bergeron RJ, Graslund A, Thelander L. Role of ribonucleotide reductase in inhibition of mammalian cell growth by potent iron chelators. J Biol Chem 1993; 268:26200-5.
6. Thelander L, Reichard P. Reduction of ribonucleotides. Annu Rev Biochem 1979; 48:133-58.
7. Lucas JJ, Szepesi A, Domenico J, Takase K, Tordai A, Terada N, Gelfand EW. Effects of iron-depletion on cell cycle progression in normal human T lymphocytes: Selective inhibition of the appearance of the cyclin A-associated component of the p33cdk2 kinase. Blood 1995; 86:2268-80.
8. 1 phase of the cell cycle. Cancer Res 1993; 53:3968-75.
9. Kwok JC, Richardson DR. The iron metabolism of neoplastic cells: Alterations that facilitate proliferation? Crit Rev Oncol Hematol 2002; 42:65-78.
10. 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.
11. Renton FJ, Jeitner TM. Cell cycle-dependent inhibition of the proliferation of human neural tumor cell lines by iron chelators. Biochem Pharmacol 1996; 51:1553-61.
12. Cook JD, SB, Baynes RD. Iron deficiency: The global perspective. Adv Exp Med Biol 1994; 356:219-28.
13. Hileti DPP, Hoffbrand AV. Iron chelators induce apoptosis in proliferating cells. Br J Haematol 1995; 89:181-7.
14. Buss JL, Torti FM, Torti SV. The role of iron chelation in cancer therapy. Curr Med Chem 2003; 10:1021-34.
15. Kalinowski DS, Richardson DR. The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacol Rev 2005; 57:547-83.
16. Dunn LL, Suryo-Rahmanto Y, Richardson DR. Iron uptake and metabolism in the new millennium. Trends Cell Biol 2007; 17:93-100.
17. Hentze MW, Muckenthaler MU, Andrews NC. Balancing acts: Molecular control of mammalian iron metabolism. Cell 2004; 117:285-97.
18. Richardson DR, Ponka P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim Biophys Acta 1997; 1331:1-40.
19. Latunde-Dada GO, Van der Westhuizen J, Vulpe CD, Anderson GJ, Simpson RJ, McKie AT. Molecular and functional roles of duodenal cytochrome B (Dcytb) in iron metabolism. Blood Cells Mol Dis 2002; 29:356-60.
20. Gunshin H, Starr CN, Direnzo C, Fleming MD, Jin J, Greer EL, Sellers VM, Galica SM, Andrews NC. Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. Blood 2005; 106:2879-83.
21. Shayeghi M, Latunde-Dada GO, Oakhill JS, Laftah AH, Takeuchi K, Halliday N, Khan Y, Warley A, McCann FE, Hider RC, Frazer DM, Anderson GJ, Vulpe CD, Simpson RJ, McKie AT. Identification of an intestinal heme transporter. Cell 2005; 122:789-801.
22. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 2006; 127:917-28.
23. Andrews NC. When is a heme transporter not a heme transporter? When it's a folate transporter. Cell Metab 2007; 5:5-6.
24. Watts RN, Ponka P, Richardson DR. Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism: Mirror-image effector molecules that target iron. Biochem J 2003; 369:429-40.
25. Harrison PM, Arosio P. The ferritins: Molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1996; 1275:161-203.
26. Richardson DR. Molecular mechanisms of iron uptake by cells and the use of iron chelators for the treatment of cancer. Curr Med Chem 2005; 12:2711-29.
27. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, Libina N, Gitschier J, Anderson GJ. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat Genet 1999; 21:195-9.
28. Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, Moynihan J, Paw BH, Drejer A, Barut B, Zapata A, Law TC, Brugnara C, Lux SE, Pinkus GS, Pinkus JL, Kingsley PD, Palis J, Fleming MD, Andrews NC, Zon LI. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 2000; 403:776-81.
29. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004; 306:2090-3.
30. Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dube MP, Andres L, MacFarlane J, Sakellaropoulos N, Politou M, Nemeth E, Thompson J, Risler JK, Zaborowska C, Babakaiff R, Radomski CC, Pape TD, Davidas O, Christakis J, Brissot P, Lockitch G, Ganz T, Hayden MR, Goldberg YP. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet 2004; 36:77-82.
31. Niederkofler V, Salie R, Arber S. Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest 2005; 115:2180-6.
32. Morgan EH. Transferrin biochemistry, physiology and clinical significance. Mol Aspects Med 1981; 4:1-123.
33. Morgan EH, Oates PS. Mechanisms and regulation of intestinal iron absorption. Blood Cells Mol Dis 2002; 29:384-99.
34. Richardson DR. Iron chelators as therapeutic agents for the treatment of cancer. Crit Rev Oncol Hematol 2002; 42:267-81.
35. Klausner RD, Ashwell G, van Renswoude J, Harford JB, Bridges KR. Binding of apotransferrin to K562 cells: Explanation of the transferrin cycle. Proc Natl Acad Sci USA 1983; 80:2263-6.
36. Ohgami RS, Campagna DR, Greer EL, Antiochos B, McDonald A, Chen J, Sharp JJ, Fujiwara Y, Barker JE, Fleming MD. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat Genet 2005; 37:1264-9.
37. Fleming MD, Trenor IIIrd CC, Su MA, Foernzler D, Beier DR, Dietrich WF, Andrews NC. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 1997; 16:383-6.
38. Kawabata H, Yang R, Hirama T, Vuong PT, Kawano S, Gombart AF, Koeffler HP. Molecular cloning of transferrin receptor 2: A new member of the transferrin receptor-like family. J Biol Chem 1999; 274:20826-32.
39. Kawabata H, Germain RS, Vuong PT, Nakamaki T, Said JW, Koeffler HP. Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo. J Biol Chem 2000; 275:16618-25.
40. Goswami T, Andrews NC. Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem 2006; 281:28494-8.
41. Mattman A, Huntsman D, Lockitch G, Langlois S, Buskard N, Ralston D, Butterfield Y, Rodrigues P, Jones S, Porto G, Marra M, De Sousa M, Vatcher G. Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: Identification of a novel TfR2 mutation. Blood 2002; 100:1075-7.
42. Hentze MW, Kuhn LC. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Natl Acad Sci USA 1996; 93:8175-82.
43. Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet 1999; 21:396-9.
44. Robb AD, Ericsson M, Wessling-Resnick M. Transferrin receptor 2 mediates a biphasic pattern of transferrin uptake associated with ligand delivery to multivesicular bodies. Am J Physiol Cell Physiol 2004; 287:C1769-75.
45. Jacobs A. Low molecular weight intracellular iron transport compounds. Blood 1977; 50:433-9.
46. Richardson DR, Ponka P, Vyoral D. Distribution of iron in reticulocytes after inhibition of heme synthesis with succinylacetone: Examination of the intermediates involved in iron metabolism. Blood 1996; 87:3477-88.
47. Ponka P, Sheftel AD, Zhang AS. Iron targeting to mitochondria in erythroid cells. Biochem Soc Trans 2002; 30:735-8.
48. Sheftel AD, Zhang AS, Brown CM, Shirihai OS, Ponka P. Direct interorganellar transfer of iron from endosome to mitochondrion. Blood 2007, [Epub ahead of print].
49. Ponka P. Tissue-specific regulation of iron metabolism and heme synthesis: Distinct control mechanisms in erythroid cells. Blood 1997; 89:1-25.
50. Napier I, Ponka P, Richardson DR. Iron trafficking in the mitochondrion: Novel pathways revealed by disease. Blood 2005; 105:1867-74.
51. Shaw GC, Cope JJ, Li L, Corson K, Hersey C, Ackermann GE, Gwynn B, Lambert AJ, Wingert RA, Traver D, Trede NS, Barut BA, Zhou Y, Minet E, Donovan A, Brownlie A, Balzan R, Weiss MJ, Peters LL, Kaplan J, Zon LI, Paw BH. Mitoferrin is essential for erythroid iron assimilation. Nature 2006; 440:96-100.
52. Levi S, Corsi B, Bosisio M, Invernizzi R, Volz A, Sanford D, Arosio P, Drysdale J. A human mitochondrial ferritin encoded by an intronless gene. J Biol Chem 2001; 276:24437-40.
53. Nie G, Sheftel AD, Kim SF, Ponka P. Overexpression of mitochondrial ferritin causes cytosolic iron depletion and changes cellular iron homeostasis. Blood 2005; 105:2161-7.
54. Eisenstein RS, Ross KL. Novel roles for iron regulatory proteins in the adaptive response to iron deficiency. J Nutr 2003; 133:1510S-6S.
55. Sanchez M, Galy B, Dandekar T, Bengert P, Vainshtein Y, Stolte J, Muckenthaler MU, Hentze MW. Iron regulation and the cell cycle: Identification of an iron-responsive element in the 3′-untranslated region of human cell division cycle 14A mRNA by a refined microarray-based screening strategy. J Biol Chem 2006; 281:22865-74.
56. Guo B, Phillips JD, Yu Y, Leibold EA. Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J Biol Chem 1995; 270:21645-51.
57. Neckers LM, Cossman J. Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci USA 1983; 80:3494-8.
58. O'Donnell KAYD, Zeller KI, Kim JW, Racke F, Thomas-Tikhonenko A, Dang CV. Activation of transferrin receptor 1 by c-Myc enhances cellular proliferation and tumorigenesis. Mol Cell Biol 2006; 26:2373-86.
59. Kalinowski DS, Richardson DR. Iron chelators and differing modes of action and toxicity: The changing face of iron chelation therapy. Chem Res Toxicol 2007; 20:715-20.
60. Larrick JW, Cresswell P. Modulation of cell surface iron transferrin receptors by cellular density and state of activation. J Supramol Struct 1979; 11:579-86.
61. Richardson DR, Baker E. The uptake of iron and transferrin by the human malignant melanoma cell. Biochim Biophys Acta 1990; 1053:1-12.
62. Richardson DR, Baker E. The effect of desferrioxamine and ferric ammonium citrate on the uptake of iron by the membrane iron-binding component of human melanoma cells. Biochim Biophys Acta 1992; 1103:275-80.
63. Elford HL, Freese M, Passamani E, Morris HP. Ribonucleotide reductase and cell proliferation. I. Variations of ribonucleotide reductase activity with tumor growth rate in a series of rat hepatomas. J Biol Chem 1970; 245:5228-33.
64. Takeda E, Weber G. Role of ribonucleotide reductase in expression in the neoplastic program. Life Sci 1981; 28:1007-14.
65. Witt L, Yap T, Blakley RL. Regulation of ribonucleotide reductase activity and its possible exploitation in chemotherapy. Adv Enzyme Regul 1978; 17:157-71.
66. Donfrancesco A, Deb G, Dominici C, Pileggi D, Castello MA, Helson L. Effects of a single course of deferoxamine in neuroblastoma patients. Cancer Res 1990; 50:4929-30.
67. Estrov Z, Tawa A, Wang XH, Dube ID, Sulh H, Cohen A, Gelfand EW, Freedman MH. In vitro and in vivo effects of deferoxamine in neonatal acute leukemia. Blood 1987; 69:757-61.
68. Kaplinsky C, Estrov Z, Freedman MH, Gelfand EW, Cohen A. Effect of deferoxamine on DNA synthesis, DNA repair, cell proliferation, and differentiation of HL-60 cells. Leukemia 1987; 1:437-41.
69. Blatt J, Taylor SR, Stitely S. Mechanism of antineuroblastoma activity of deferoxamine in vitro. J Lab Clin Med 1988; 112:433-6.
70. Blatt J, Stitely S. Antineuroblastoma activity of desferoxamine in human cell lines. Cancer Res 1987; 47:1749-50.
71. Richardson D, Ponka P, Baker E. The effect of the iron(III) chelator, desferrioxamine, on iron and transferrin uptake by the human malignant melanoma cell. Cancer Res 1994; 54:685-9.
72. Darnell G, Richardson DR. 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 1999; 94:781-92.
73. Yu Y, Wong J, Lovejoy DB, Kalinowski DS, Richardson DR. Chelators at the cancer coalface: Desferrioxamine to Triapine and beyond. Clin Cancer Res 2006; 12:6876-83.
74. Finch RA, Liu M, Grill SP, Rose WC, Loomis R, Vasquez KM, Cheng Y, Sartorelli AC. Triapine (3-aminopyridine-2-carboxaldehyde- thiosemicarbazone): A potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity. Biochem Pharmacol 2000; 59:983-91.
75. Torti SV, Torti FM, Whitman SP, Brechbiel MW, Park G, Planalp RP. Tumor cell cytotoxicity of a novel metal chelator. Blood 1998; 92:1384-9.
76. Rakba N, Loyer P, Gilot D, Delcros JG, Glaise D, Baret P, Pierre JL, Brissot P, Lescoat G. Antiproliferative and apoptotic effects of O-Trensox, a new synthetic iron chelator, on differentiated human hepatoma cell lines. Carcinogenesis 2000; 21:943-51.
77. Ponka P, Borova J, Neuwirt J, Fuchs O. Mobilization of iron from reticulocytes: Identification of pyridoxal isonicotinoyl hydrazone as a new iron chelating agent. FEBS Lett 1979; 97:317-21.
78. Ponka P, Borova J, Neuwirt J, Fuchs O, Necas E. A study of intracellular iron metabolism using pyridoxal isonicotinoyl hydrazone and other synthetic chelating agents. Biochim Biophys Acta 1979; 586:278-97.
79. Richardson DR, Tran EH, Ponka P. The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents. Blood 1995; 86:4295-306.
80. Chaston TB, Watts RN, Yuan J, Richardson DR. Potent antitumor activity of novel iron chelators derived from di-2-pyridylketone isonicotinoyl hydrazone involves fenton-derived free radical generation. Clin Cancer Res 2004; 10:7365-74.
81. Becker E, Lovejoy DB, Greer J, Watts R, Richardson DR. Novel aroylhydrazone iron chelators differ in their iron chelation efficacy and anti-proliferative activity: Identification of a new class of potential anti-proliferative agents. Br J Pharmacol 2003; 138:819-30.
82. Kalinowski DS, Yu Y, Sharpe PS, Mohammad Islam M, Liao YT, Lovejoy DB, Kumar N, Bernhardt PV, Richardson DR. Design, synthesis and characterization of novel iron chelators: Structure-activity relationships of the 2-benzoylpyridine thiosemicarbazone series and their 3-nitrobenzoyl analogs as potent anti-tumor agents. J Med Chem 2007, (In Press).
83. Lovejoy DB, Richardson DR. Novel "hybrid" iron chelators derived from aroylhydrazones and thiosemicarbazones demonstrate high anti-proliferative activity that is selective for tumor cells. Blood 2002; 100:666-76.
84. Whitnall M, Howard J, Ponka P, Richardson DR. A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proc Natl Acad Sci USA 2006; 103:14901-6.
85. Yen Y, Margolin K, Doroshow J, Fishman M, Johnson B, Clairmont C, Sullivan D, Sznol M. A phase I trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in combination with gemcitabine for patients with advanced cancer. Cancer Chemother Pharmacol 2004; 54:331-42.
86. Yee KW, Cortes J, Ferrajoli A, Garcia-Manero G, Verstovsek S, Wierda W, Thomas D, Faderl S, King I, O'Brien SM, Jeha S, Andreeff M, Cahill A, Sznol M, Giles FJ. Triapine and cytarabine is an active combination in patients with acute leukemia or myelodysplastic syndrome. Leuk Res 2006; 30:813-22.
87. Gojo I, Tidwell ML, Greer J, Takebe N, Seiter K, Pochron MF, Johnson B, Sznol M, Karp JE. Phase I and pharmacokinetic study of Triapine((R)), a potent ribonucleotide reductase inhibitor, in adults with advanced hematologic malignancies. Leuk Res 2007; 31:1173-81.
88. 2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation. Blood 2005; 106:3191-9.
89. Richardson DR, Bernhardt PV. Crystal and molecular structure of 2-hydroxy-1-naphthyl-aldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: An iron chelator with anti-proliferative activity. J Biol Inorg Chem 1999; 4:266-73.
90. Richardson DR, Milnes K. The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents II: The mechanism of action of ligands derived from salicylaldehyde benzoyl hydrazone and 2-hydroxy-1-naphthylaldehyde benzoyl hydrazone. Blood 1997; 89:3025-38.
91. Green DA, Antholine WE, Wong SJ, Richardson DR, Chitambar CR. Inhibition of malignant cell growth by 311, a novel iron chelator of the pyridoxal isonicotinoyl hydrazone class: Effect on the R2 subunit of ribonucleotide reductase. Clin Cancer Res 2001; 7:3574-9.
92. Becker EM, Lovejoy DB, Greer JM, Watts R, Richardson DR. Identification of the di-pyridyl ketone isonicotinoyl hydrazone (PKIH) analogues as potent iron chelators and anti-tumour agents. Br J Pharmacol 2003; 138:819-30.
93. Yuan J, Lovejoy DB, Richardson DR. Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: In vitro and in vivo assessment. Blood 2004; 104:1450-8.
94. Richardson DR, Sharpe PC, Lovejoy DB, Senaratne D, Kalinowski DS, Islam M, Bernhardt PV. Dipyridyl thiosemicarbazone chelators with potent and selective anti-tumor activity form iron complexes with marked redox activity. J Med Chem 2006; 49:6510-21.
95. Boldt DH. New perspectives on iron: An introduction. Am J Med Sci 1999; 318:207-12.
96. 1 phase progression: Cycling on cue. Cell 1994; 79:551-5.
97. Zetterberg A, Larsson O, Wiman KG. What is the restriction point? Curr Opin Cell Biol 1995; 7:835-42.
98. Golias CH, Charalabopoulos A, Charalabopoulos K. Cell proliferation and cell cycle control: A mini review. Int J Clin Pract 2004; 58:1134-41.
99. 1-phase progression. Genes Dev 1999; 13:1501-12.
100. 1/S transition. Cancer Surv 1997; 29:7-23.
101. Gao J, Richardson DR. 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 2001; 98:842-50.
102. Le NT, Richardson DR. 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 2004; 104:2967-75.
103. Kulp KS, Green SL, Vulliet PR. Iron deprivation inhibits cyclin-dependent kinase activity and decreases cyclin D/CDK4 protein levels in asynchronous MDA-MB-453 human breast cancer cells. Exp Cell Res 1996; 229:60-8.
104. Ashcroft M, Taya Y, Vousden KH. Stress signals utilize multiple pathways to stabilize p53. Mol Cell Biol 2000; 20:3224-33.
105. Fukuchi K, Tomoyasu S, Watanabe H, Kaetsu S, Tsuruoka N, Gomi K. Iron deprivation results in an increase in p53 expression. Biol Chem Hoppe Seyler 1995; 376:627-30.
106. Liang SX, Richardson DR. 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 2003; 24:1601-14.
107. Fu D, Richardson DR. Iron chelation and regulation of the cell-cycle: Two mechanisms of post-transcriptional regulation of the universal cyclin-dependent kinase inhibitor p21CIP1/WAF1 by iron depletion. Blood 2007, [Epub ahead of print].
108. 1 by enhancing the levels of p27(Kip1). Exp Cell Res 2000; 254:64-71.
109. Wang G, Miskimins R, Miskimins WK. Regulation of p27(Kip1) by intracellular iron levels. Biometals 2004; 17:15-24.
110. Dong Z, Arnold RJ, Yang Y, Park MH, Hrncirova P, Mechref Y, Novotny MV, Zhang JT. Modulation of differentiation-related gene 1 expression by cell cycle blocker mimosine, revealed by proteomic analysis. Mol Cell Proteomics 2005; 4:993-1001.
111. Terada N, Lucas JJ, Gelfand EW. Differential regulation of the tumor suppressor molecules, retinoblastoma susceptibility gene product (Rb) and p53, during cell cycle progression of normal human T cells. J Immunol 1991; 147:698-704.
112. Jordan A, Reichard P. Ribonucleotide reductases. Annu Rev Biochem 1998; 67:71-98.
113. Reichard P. From RNA to DNA, why so many ribonucleotide reductases? Science 1993; 260:1773-7.
114. Jordan A, Pontis E, Atta M, Krook M, Gibert I, Barbe J, Reichard P. A second class I ribonucleotide reductase in Enterobacteriaceae: Characterization of the Salmonella typhimurium enzyme. Proc Natl Acad Sci USA 1994; 91:12892-6.
115. Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, Matsui K, Takei Y, Nakamura Y. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 2000; 404:42-9.
116. Byun DS, Chae KS, Ryu BK, Lee MG, Chi SG. Expression and mutation analyses of P53R2, a newly identified p53 target for DNA repair in human gastric carcinoma. Int J Cancer 2002; 98:718-23.
117. Nakano K, Balint E, Ashcroft M, Vousden KH. A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene 2000; 19:4283-9.
118. Shao J, Zhou B, Zhu L, Qiu W, Yuan YC, Xi B, Yen Y. In vitro characterization of enzymatic properties and inhibition of the p53R2 subunit of human ribonucleotide reductase. Cancer Res 2004; 64:1-6.
119. Tsimberidou AM, Alvarado Y, Giles FJ. Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies. Expert Rev Anticancer Ther 2002; 2:437-48.
120. Chaston TB, Lovejoy DB, Watts RN, Richardson DR. 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 2003; 9:402-14.
121. Sartorelli AC, Agrawal KC, Moore EC. Mechanism of inhibition of ribonucleoside diphosphate reductase by a-(N)-heterocyclic aldehyde thiosemicarbazones. Biochem Pharmacol 1971; 20:3119-23.
122. Simonart T, Degraef C, Andrei G, Mosselmans R, Hermans P, Van Vooren JP, Noel JC, Boelaert JR, Snoeck R, Heenen M. Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. J Invest Dermatol 2000; 115:893-900.
123. 1/S phase transition. Nat Cell Biol 2005; 7:831-6.
124. Kaldis P, Aleem E. Cell cycle sibling rivalry: Cdc2 vs Cdk2. Cell Cycle 2005; 4:1491-4.
125. Nurtjahja-Tjendraputra E, Fu D, Phang JM, Richardson DR. Iron chelation regulates cyclin D1 expression via the proteasome: A link to iron deficiency-mediated growth suppression. Blood 2007; 109:4045-54.
126. Burnworth B, Popp S, Stark HJ, Steinkraus V, Brocker EB, Hartschuh W, Birek C, Boukamp P. Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation. Oncogene 2006; 25:4399-412.
127. Donnellan RC, R. Cyclin D1 and human neoplasia. Mol Pathol 1998; 51:1-7.
128. Schrump DS, CA, Consoli U. Inhibition of lung cancer proliferation by antisense cyclin D. Cancer Gene Ther 1996; 3:131-5.
129. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991; 253:49-53.
130. Hatakeyama M, Weinberg RA. The role of RB in cell cycle control. Prog Cell Cycle Res 1995; 1:9-19.
131. Weinberg RA. The retinoblastoma protein and cell cycle control. Cell 1995; 81:323-30.
132. Abeysinghe RD, Greene BT, Haynes R, Willingham MC, Turner J, Planalp RP, Brechbiel MW, Torti FM, Torti SV. p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron chelator. Carcinogenesis 2001; 22:1607-14.
133. Sun Y, Bian J, Wang Y, Jacobs C. Activation of p53 transcriptional activity by 1,10-phenanthroline, a metal chelator and redox sensitive compound. Oncogene 1997; 14:385-93.
134. 1 cyclin-dependent kinases. Cell 1993; 75:805-16.
135. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75:817-25.
136. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 is a universal inhibitor of cyclin kinases. Nature 1993; 366:701-4.
137. Luo Y, Hurwitz J, Massague J. Cell-cycle inhibition by independent CDK and PCNA binding domains in p21Cip1. Nature 1995; 375:159-61.
138. Waga S, Hannon GJ, Beach D, Stillman B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 1994; 369:574-8.
139. Vidal A, Koff A. Cell-cycle inhibitors: Three families united by a common cause. Gene 2000; 247:1-15.
140. Delavaine L, La Thangue NB. Control of E2F activity by p21Waf1/Cip1. Oncogene 1999; 18:5381-92.
141. Kitaura H, Shinshi M, Uchikoshi Y, Ono T, Iguchi-Ariga SM, Ariga H. Reciprocal regulation via protein-protein interaction between c-Myc and p21(cip1/waf1/sdi1) in DNA replication and transcription. J Biol Chem 2000; 275:10477-83.
142. Cheng M, Olivier P, Diehl JA, Fero M, Roussel MF, Roberts JM, Sherr CJ. The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. Embo J 1999; 18:1571-83.
143. Weiss RH. p21Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell 2003; 4:425-9.
144. Weiss RH, Marshall D, Howard L, Corbacho AM, Cheung AT, Sawai ET. Suppression of breast cancer growth and angiogenesis by an antisense oligodeoxynucleotide to p21(Waf1/Cip1). Cancer Lett 2003; 189:39-48.
145. Gartel AL, Tyner AL. Transcriptional regulation of the p21((WAF1/CIP1)) gene. Exp Cell Res 1999; 246:280-9.
146. Wajapeyee N, Somasundaram K. Cell cycle arrest and apoptosis induction by activator protein 2alpha (AP-2alpha) and the role of p53 and p21WAF1/CIP1 in AP-2alpha-mediated growth inhibition. J Biol Chem 2003; 278:52093-101.
147. Tvrdik D, Dundr P, Povysil C, Pytlik R, Plankova M. Up-regulation of p21WAF1 expression is mediated by Sp1/Sp3 transcription factors in TGFbeta1-arrested malignant B cells. Med Sci Monit 2006; 12:BR227-34.
148. Le NT, Richardson DR. Potent iron chelators increase the mRNA levels of the universal cyclin-dependent kinase inhibitor p21(CIP1/WAF1), but paradoxically inhibit its translation: A potential mechanism of cell cycle dysregulation. Carcinogenesis 2003; 24:1045-58.
149. Asher G, Bercovich Z, Tsvetkov P, Shaul Y, Kahana C. 20S proteasomal degradation of ornithine decarboxylase is regulated by NQO1. Mol Cell 2005; 17:645-55.
150. Newman RMA, Mangold U, Koike C, Diah S, Schmidt M, Finely D, Zetter BR. Antizyme targets cyclin D1 for degradation. J Biol Chem 2004; 279:41504-11.
151. Coleman ML, Marshall CJ, Olson MF. Ras promotes p21(Waf1/Cip1) protein stability via a cyclin D1-imposed block in proteasome-mediated degradation. Embo J 2003; 22:2036-46.
152. Gazitt Y, Reddy SV, Alcantara O, Yang J, Boldt DH. A new molecular role for iron in regulation of cell cycling and differentiation of HL-60 human leukemia cells: Iron is required for transcription of p21(WAF1/CIP1) in cells induced by phorbol myristate acetate. J Cell Physiol 2001; 187:124-35.
153. 1 accumulation caused by iron deprivation with deferoxamine does not accompany change of pRB status in ML-1 cells. Biochim Biophys Acta 1997; 1357:297-305.
154. Fan YBA, Weiss RH. An antisense oligodeoxynucleotide to p21(Waf1/Cip1) causes apoptosis in human breast cancer cells. Mol Cancer Ther 2003; 2:773-82.
155. Dong Z, Zhang JT. EIF3 p170, a mediator of mimosine effect on protein synthesis and cell cycle progression. Mol Biol Cell 2003; 14:3942-51.
156. Yoon G, Kim HJ, Yoon YS, Cho H, Lim IK, Lee JH. Iron chelation-induced senescence-like growth arrest in hepatocyte cell lines: Association of transforming growth factor beta1 (TGF-beta1)mediated p27Kip1 expression. Biochem J 2002; 366:613-21.
157. Carlson SG, Fawcett TW, Bartlett JD, Bernier M, Holbrook NJ. Regulation of the C/EBP-related gene gadd153 by glucose deprivation. Mol Cell Biol 1993; 13:4736-44.
158. Abcouwer SF, Schwarz C, Meguid RA. Glutamine deprivation induces the expression of GADD45 and GADD153 primarily by mRNA stabilization. J Biol Chem 1999; 274:28645-51.
159. Fanzo JC, Reaves SK, Cui L, Zhu L, Wu JY, Wang YR, Lei KY. Zinc status affects p53, gadd45, and c-fos expression and caspase-3 activity in human bronchial epithelial cells. Am J Physiol Cell Physiol 2001; 281:C751-7.
160. Oh-Hashi K, Maruyama W, Isobe K. Peroxynitrite induces GADD34, 45, and 153 VIA p38 MAPK in human neuroblastoma SH-SY5Y cells. Free Radic Biol Med 2001; 30:213-21.
161. Zerbini LF, Libermann TA. GADD45 deregulation in cancer: Frequently methylated tumor suppressors and potential therapeutic targets. Clin Cancer Res 2005; 11:6409-13.
162. Kearsey JM, Coates PJ, Prescott AR, Warbrick E, Hall PA. Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1. Oncogene 1995; 11:1675-83.
163. 2/M cell cycle checkpoints induced by genotoxic stress. J Cell Physiol 2002; 192:327-38.
164. Bulavin DV, Kovalsky O, Hollander MC, Fornace Jr AJ. Loss of oncogenic H-ras-induced cell cycle arrest and p38 mitogen-activated protein kinase activation by disruption of Gadd45a. Mol Cell Biol 2003; 23:3859-71.
165. Hollander MC, Sheikh MS, Yu K, Zhan Q, Iglesias M, Woodworth C, Fornace Jr AJ. Activation of Gadd34 by diverse apoptotic signals and suppression of its growth inhibitory effects by apoptotic inhibitors. Int J Cancer 2001; 96:22-31.
166. Maytin EV, Ubeda M, Lin JC, Habener JF. Stress-inducible transcription factor CHOP/gadd153 induces apoptosis in mammalian cells via p38 kinase-dependent and -independent mechanisms. Exp Cell Res 2001; 267:193-204.
167. Zhan Q, Lord KA, Alamo Jr I, Hollander MC, Carrier F, Ron D, Kohn KW, Hoffman B, Liebermann DA, Fornace Jr AJ. The gadd and MyD genes define a novel set of mammalian genes encoding acidic proteins that synergistically suppress cell growth. Mol Cell Biol 1994; 14:2361-71.
168. Price BD, Calderwood SK. Gadd45 and Gadd153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose-regulated proteins. Cancer Res 1992; 52:3814-7.
169. Lee SK, Jang HJ, Lee HJ, Lee J, Jeon BH, Jun CD, Kim EC. p38 and ERK MAP kinase mediates iron chelator-induced apoptosis and -suppressed differentiation of immortalized and malignant human oral keratinocytes. Life Sci 2006; 79:1419-27.
170. Pruitt K, Pruitt WM, Bilter GK, Westwick JK, Der CJ. Raf-independent deregulation of p38 and JNK mitogen-activated protein kinases are critical for Ras transformation. J Biol Chem 2002; 277:31808-17.
171. Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, Appella E, Fornace Jr AJ. Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. Embo J 1999; 18:6845-54.
172. Lavoie JN, L'Allemain G, Brunet A, Muller R, Pouyssegur J. Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J Biol Chem 1996; 271:20608-16.
173. 1 phase cell cycle arrest in vascular smooth muscle cells through inducing p21Cip1 expression: Involvement of p38 mitogen activated protein kinase. J Cell Physiol 2004; 198:310-23.
174. Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 1999; 15:551-78.
175. Greijer AE, van der Groep P, Kemming D, Shvarts A, Semenza GL, Meijer GA, van de Wiel MA, Belien JA, van Diest PJ, van der Wall E. Up-regulation of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor 1 (HIF-1). J Pathol 2005; 206:291-304.
176. Wang GL, Jiang BH, 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; 92:5510-4.
177. Stockmann C, Fandrey J. Hypoxia-induced erythropoietin production: A paradigm for oxygen-regulated gene expression. Clin Exp Pharmacol Physiol 2006; 33:968-79.
178. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin Jr WG. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science 2001; 292:464-8.
179. Caro J. Hypoxia regulation of gene transcription. High Alt Med Biol 2001; 2:145-54.
180. Bianchi L, Tacchini L, Cairo G. HIF-1-mediated activation of transferrin receptor gene transcription by iron chelation. Nucleic Acids Res 1999; 27:4223-7.
181. Tacchini L, Bianchi L, Bernelli-Zazzera A, Cairo G. Transferrin receptor induction by hypoxia: HIF-1-mediated transcriptional activation and cell-specific post-transcriptional regulation. J Biol Chem 1999; 274:24142-6.
182. Kovacevic Z, Richardson DR. The metastasis suppressor, Ndrg-1: A new ally in the fight against cancer. Carcinogenesis 2006; 27:2355-66.
183. Guan RJ, Ford HL, Fu Y, Li Y, Shaw LM, Pardee AB. Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Cancer Res 2000; 60:749-55.
184. Kurdistani SK, Arizti P, Reimer CL, Sugrue MM, Aaronson SA, Lee SW. Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage. Cancer Res 1998; 58:4439-44.
185. An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM. Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature 1998; 392:405-8.
186. Bruick RK. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci USA 2000; 97:9082-7.
187. Guo K, Searfoss G, Krolikowski D, Pagnoni M, Franks C, Clark K, Yu KT, Jaye M, Ivashchenko Y. Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ 2001; 8:367-76.
188. Furukawa T, Adachi Y, Fujisawa J, Kambe T, Yamaguchi-Iwai Y, Sasaki R, Kuwahara J, Ikehara S, Tokunaga R, Taketani S. Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines. Oncogene 2001; 20:4718-27.
189. Mizutani A, Furukawa T, Adachi Y, Ikehara S, Taketani S. A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein Nip3, leading to cellular apoptosis. J Biol Chem 2002; 277:15851-8.
190. Le NT, Richardson DR. Competing pathways of iron chelation: Angiogenesis or anti-tumor activity: Targeting different molecules to induce specific effects. Int J Cancer 2004; 110:468-9.
191. Stein S, Thomas EK, Herzog B, Westfall MD, Rocheleau JV, Jackson IInd RS, Wang M, Liang P. NDRG1 is necessary for p53-dependent apoptosis. J Biol Chem 2004; 279:48930-40.
192. Bandyopadhyay S, Pai SK, Gross SC, Hirota S, Hosobe S, Miura K, Saito K, Commes T, Hayashi S, Watabe M, Watabe K. The Drg-1 gene suppresses tumor metastasis in prostate cancer. Cancer Res 2003; 63:1731-6.
193. Bandyopadhyay S, Pai SK, Hirota S, Hosobe S, Takano Y, Saito K, Piquemal D, Commes T, Watabe M, Gross SC, Wang Y, Ran S, Watabe K. Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression. Oncogene 2004; 23:5675-81.
194. Maruyama Y, Ono M, Kawahara A, Yokoyama T, Basaki Y, Kage M, Aoyagi S, Kinoshita H, Kuwano M. Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis. Cancer Res 2006; 66:6233-42.
195. Bandyopadhyay S, Wang Y, Zhan R, Pai SK, Watabe M, Iiizumi M, Furuta E, Mohinta S, Liu W, Hirota S, Hosobe S, Tsukada T, Miura K, Takano Y, Saito K, Commes T, Piquemal D, Hai T, Watabe K. The tumor metastasis suppressor gene Drg-1 down-regulates the expression of activating transcription factor 3 in prostate cancer. Cancer Res 2006; 66:11983-90.
196. Iyengar P, Combs TP, Shah SJ, Gouon-Evans V, Pollard JW, Albanese C, Flanagan L, Tenniswood MP, Guha C, Lisanti MP, Pestell RG, Scherer PE. Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 2003; 22:6408-23.
197. Janz M, Hummel M, Truss M, Wollert-Wulf B, Mathas S, Johrens K, Hagemeier C, Bommert K, Stein H, Dorken B, Bargou RC. Classical Hodgkin lymphoma is characterized by high constitutive expression of activating transcription factor 3 (ATF3), which promotes viability of Hodgkin/Reed-Sternberg cells. Blood 2006; 107:2536-9.
198. Ameri K, Hammond EM, Culmsee C, Raida M, Katschinski DM, Wenger RH, Wagner E, Davis RJ, Hai T, Denko N, Harris AL. Induction of activating transcription factor 3 by anoxia is independent of p53 and the hypoxic HIF signalling pathway. Oncogene 2007; 26:284-9.
199. Kaiser BK, Zimmerman ZA, Charbonneau H, Jackson PK. Disruption of centrosome structure, chromosome segregation, and cytokinesis by misexpression of human Cdc14A phosphatase. Mol Biol Cell 2002; 13:2289-300.
200. Lawen A. Apoptosis-an introduction. Bioessays 2003; 25:888-96.
201. Fornace Jr AJ, Jackman J, Hollander MC, Hoffman-Liebermann B, Liebermann DA. Genotoxic-stress-response genes and growth-arrest genes: Gadd, MyD, and other genes induced by treatments eliciting growth arrest. Ann NY Acad Sci 1992; 663:139-53.
202. Brard L, Granai CO, Swamy N. Iron chelators deferoxamine and diethylenetriamine pentaacetic acid induce apoptosis in ovarian carcinoma. Gynecol Oncol 2006; 100:116-27.
203. Fan L, Iyer J, Zhu S, Frick KK, Wada RK, Eskenazi AE, Berg PE, Ikegaki N, Kennett RH, Frantz CN. Inhibition of N-myc expression and induction of apoptosis by iron chelation in human neuroblastoma cells. Cancer Res 2001; 61:1073-9.
204. Simonart T, Boelaert JR, Mosselmans R, Andrei G, Noel JC, De Clercq E, Snoeck R. Antiproliferative and apoptotic effects of iron chelators on human cervical carcinoma cells. Gynecol Oncol 2002; 85:95-102.
205. Alvero AB, Chen W, Sartorelli AC, Schwartz P, Rutherford T, Mor G. Triapine (3-amino-pyridine-2-carboxaldehyde thiosemicarbazone) induces apoptosis in ovarian cancer cells. J Soc Gynecol Investig 2006; 13:145-52.
206. Greene BT, Thorburn J, Willingham MC, Thorburn A, Planalp RP, Brechbiel MW, Jennings-Gee J, Wilkinson JT, Torti FM, Torti SV. Activation of caspase pathways during iron chelator-mediated apoptosis. J Biol Chem 2002; 277:25568-75.
207. Zhao R, Planalp RP, Ma R, Greene BT, Jones BT, Brechbiel MW, Torti FM, Torti SV. Role of zinc and iron chelation in apoptosis mediated by tachpyridine, an anti-cancer iron chelator. Biochem Pharmacol 2004; 67:1677-88.
208. Rakba N, Aouad F, Henry C, Caris C, Morel I, Baret P, Pierre JL, Brissot P, Ward RJ, Lescoat G, Crichton RR. Iron mobilisation and cellular protection by a new synthetic chelator O-Trensox. Biochem Pharmacol 1998; 55:1797-806.
209. Amundson SA, Myers TG, Fornace Jr AJ. Roles for p53 in growth arrest and apoptosis: Putting on the brakes after genotoxic stress. Oncogene 1998; 17:3287-99.
210. LaCasse EC, Baird S, Korneluk RG, MacKenzie AE. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 1998; 17:3247-59.
211. Wang D, Liu YF, Wang YC. Deferoxamine induces apoptosis of HL-60 cells by activating caspase-3. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006; 14:485-7.
212. Kubli DA, Ycaza JE, Gustafsson AB. Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak. Biochem J 2007.