Iron chelators with topoisomerase-inhibitory activity and their anticancer applications

Antioxidants and Redox Signaling

Volumn 18, Issue 8, 2013, Pages 930-955

  Rao, V Ashutosh ^a  

^a Office of Biotechnology Products   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2 BIS(3,5 DIOXOPIPERAZIN 1 YL)ETHANE; 1,2 PROPANEDIAMINE N,N' DIACETAMIDE N,N' DIACETIC ACID; 2,3 BIS(3,5 DIOXO 1 PIPERAZINYL)BUTANE; 3 AMINOPICOLINALDEHYDE THIOSEMICARBAZONE; ACETYLCYSTEINE; ALPHA TOCOPHEROL; ANTHRACYCLINE; ASCORBIC ACID; CAROTENOID; CURCUMIN; DI 2 PYRIDYLKETONE 4,4 DIMETHYL 3 THIOSEMICARBAZONE; DNA TOPOISOMERASE; DNA TOPOISOMERASE 2 ALPHA; DNA TOPOISOMERASE INHIBITOR; DOXORUBICIN; FERROCENE; FLAVONOID; ICRF 194; IRON; IRON CHELATING AGENT; ISOXANTRONE; MITOXANTRONE; OXANTHRAZOLE; POLYPHENOL; RAZOXANE; REACTIVE OXYGEN METABOLITE; RETINOL; SILIBININ; THIOSEMICARBAZONE 24; TSC 24; UBIQUINONE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER RESISTANCE; CARDIOMYOPATHY; CARDIOTOXICITY; CELL CYCLE ARREST; CYTOPATHOGENIC EFFECT; DNA DAMAGE; DRUG EFFICACY; DRUG MECHANISM; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; HEART PROTECTION; HUMAN; IRON CHELATION; IRON METABOLISM; IRON TRANSPORT; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANTINEOPLASTIC AGENTS; CARDIOTONIC AGENTS; DNA TOPOISOMERASES; HUMANS; IRON; IRON CHELATING AGENTS; NEOPLASMS; TOPOISOMERASE INHIBITORS;

EID: 84873806976     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2012.4877     Document Type: Review

References (308)

1. Abou El Hassan MA, Heijn M, Rabelink MJ, van der Vijgh WJ, Bast A, and Hoeben RC. The protective effect of cardiac gene transfer of CuZn-sod in comparison with the cardio-protector monohydroxyethylrutoside against doxorubicin-induced cardiotoxicity in cultured cells. Cancer Gene Ther 10: 270-277, 2003.
2. Abou-El-Hassan MA, Rabelink MJ, van der Vijgh WJ, Bast A, and Hoeben RC. A comparative study between catalase gene therapy and the cardioprotector monohydroxyethyl-rutoside (MonoHER) in protecting against doxorubicin-induced cardiotoxicity in vitro. Br J Cancer 89: 2140-2146, 2003.
3. Aisen P, Wessling-Resnick M, and Leibold EA. Iron metabolism. Curr Opin Chem Biol 3: 200-206, 1999.
4. Akimitsu N, Adachi N, Hirai H, Hossain MS, Hamamoto H, Kobayashi M, Aratani Y, Koyama H, and Sekimizu K. Enforced cytokinesis without complete nuclear division in embryonic cells depleting the activity of DNA topoisome-rase IIalpha. Genes Cells 8: 393-402, 2003.
5. Aluise CD, Miriyala S, Noel T, Sultana R, Jungsuwadee P, Taylor TJ, Cai J, Pierce WM, Vore M, Moscow JA, St. Clair DK, and Butterfield DA. 2-Mercaptoethane sulfonate prevents doxorubicin-induced plasma protein oxidation and TNF-alpha release: implications for the reactive oxygen species-mediated mechanisms of chemobrain. Free Radic Biol Med 50: 1630-1638, 2011.
6. Ambroz HB, Kemp TJ, Rodger A, and Przybytniak Gy. Ferric and ferrous ions: binding to DNA and influence on radiation-induced processes. Radiat Phys Chem 71: 1023-1030, 2004.
7. Andoh T and Ishida R. Catalytic inhibitors of DNA topoi-somerase II. Biochim Biophys Acta 1400: 155-171, 1998.
8. Andrews NC and Levy JE. Iron is hot: an update on the path-ophysiology of hemochromatosis. Blood 92: 1845-1851, 1998.
9. Avondoglio D, Scott T, Kil WJ, Sproull M, Tofilon PJ, and Camphausen K. High throughput evaluation of gamma-H2AX. Radiat Oncol 4: 31, 2009.
10. Barnabe N, Zastre JA, Venkataram S, and Hasinoff BB. Deferiprone protects against doxorubicin-induced myocyte cytotoxicity. Free Radic Biol Med 33: 266-275, 2002.
11. Bast A, Haenen GR, Bruynzeel AM, and Van der Vijgh WJ. Protection by flavonoids against anthracycline cardiotoxi-city: from chemistry to clinical trials. Cardiovasc Toxicol 7: 154-159, 2007.
12. Beckford FA, Thessing J, Shaloski M, Jr., Mbarushimana PC, Brock A, Didion J, Woods J, Gonzalez-Sarrias A, and Seeram NP. Synthesis and characterization of mixed-ligand diimine-piperonal thiosemicarbazone complexes of ruthe-nium(II): biophysical investigations and biological evaluation as anticancer and antibacterial agents. J Mol Struct 992: 39-47, 2011.
13. Berger JM, Gamblin SJ, Harrison SC, and Wang JC. Structure and mechanism of DNA topoisomerase II. Nature 379: 225-232, 1996.
14. Besold AN, Lee SJ, Michel SL, Sue NL, and Cymet HJ. Functional characterization of iron-substituted neural zinc finger factor 1: metal and DNA binding. J Biol Inorg Chem 15: 583-590, 2010.
15. Bleijlevens B, Shivarattan T, Flashman E, Yang Y, Simpson PJ, Koivisto P, Sedgwick B, Schofield CJ, and Matthews SJ. Dynamic states of the DNA repair enzyme AlkB regulate product release. EMBO Rep 9: 872-877, 2008.
16. Bonadonna G, Monfardini S, De Lena M, Fossati-Bellani F, and Beretta G. Phase I and preliminary phase II evaluation of adriamycin (NSC 123127). Cancer Res 30: 2572-2582, 1970.
17. Boonsong A, Marsh S, Rooney PH, Stevenson DA, Cassidy J, and McLeod HL. Characterization of the topoisomerase I locus in human colorectal cancer. Cancer Genet Cytogenet 121: 56-60, 2000.
18. Brockman RW, Thomson JR, Bell MJ, and Skipper HE. Observations on the antileukemic activity of pyridine-2-carboxaldehyde thiosemicarbazone and thiocarbohy-drazone. Cancer Res 16: 167-170, 1956.
19. Brodie C, Siriwardana G, Lucas J, Schleicher R, Terada N, Szepesi A, Gelfand E, and Seligman P. Neuroblastoma sensitivity to growth inhibition by deferrioxamine: evidence for a block in G1 phase of the cell cycle. Cancer Res 53: 3968-3975, 1993.
20. Burgess DJ, Doles J, Zender L, Xue W, Ma B, McCombie WR, Hannon GJ, Lowe SW, and Hemann MT. Topoi-somerase levels determine chemotherapy response in vitro and in vivo. Proc Natl Acad Sci USA 105: 9053-9058, 2008.
21. Capranico G, Tinelli S, Austin CA, Fisher ML, and Zunino F. Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta 1132: 43-48, 1992.
22. Castino R, Fiorentino I, Cagnin M, Giovia A, and Isidoro C. Chelation of lysosomal iron protects dopaminergic SH-SY5Y neuroblastoma cells from hydrogen peroxide toxicity by precluding autophagy and Akt dephosphorylation. Toxicol Sci 123: 523-541, 2011.
23. Champoux JJ. Structure-based analysis of the effects of camptothecin on the activities of human topoisomerase I. Ann N Y Acad Sci 922: 56-64, 2000.
24. Champoux JJ. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 70: 369-413, 2001.
25. Chaston TB and Richardson DR. Interactions of the pyri-dine-2- carboxaldehyde isonicotinoyl hydrazone class of chelators with iron and DNA: implications for toxicity in the treatment of iron overload disease. J Biol Inorg Chem 8: 427-438, 2003.
26. Chen S, Deng PS, Bailey JM, and Swiderek KM. A two-domain structure for the two subunits of NAD(P)H:qui-none acceptor oxidoreductase. Protein Sci 3: 51-57, 1994.
27. Cheneval D, Muller M, Toni R, Ruetz S, and Carafoli E. Adriamycin as a probe for the transversal distribution of cardiolipin in the inner mitochondrial membrane. J Biol Chem 260: 13003-13007, 1985.
28. Choi HS, Park ES, Kang HJ, Shin HY, Noh CI, Yun YS, Ahn HS, and Choi JY. Dexrazoxane for preventing anthracycline cardiotoxicity in children with solid tumors. J Korean Med Sci 25: 1336-1342, 2010.
29. Christofferson DE and Yuan J. Cyclophilin A release as a biomarker of necrotic cell death. Cell Death Differ 17: 1942-1943, 2010.
30. Conklin KA. Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr Cancer 37: 1-18, 2000.
31. Conklin KA. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther 3: 294-300, 2004.
32. Conte D, Narindrasorasak S, and Sarkar B. In vivo and in vitro iron-replaced zinc finger generates free radicals and causes DNA damage. J Biol Chem 271: 5125-5130, 1996.
33. Coon JS, Marcus E, Gupta-Burt S, Seelig S, Jacobson K, Chen S, Renta V, Fronda G, and Preisler HD. Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer. Clin Cancer Res 8: 1061-1067, 2002.
34. Cooper JB, McIntyre K, Badasso MO, Wood SP, Zhang Y, Garbe TR, and Young D. X-ray structure analysis of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis at 2.0 Angstroms resolution reveals novel dimer-dimer interactions. J Mol Biol 246: 531-544, 1995.
35. Corbett AH and Osheroff N. When good enzymes go bad: conversion of topoisomerase II to a cellular toxin by anti-neoplastic drugs. Chem Res Toxicol 6: 585-597, 1993.
36. Cornarotti M, Tinelli S, Willmore E, Zunino F, Fisher LM, Austin CA, and Capranico G. Drug sensitivity and sequence specificity of human recombinant DNA topoi-somerases IIalpha (p170) and IIbeta (p180). Mol Pharmacol 50: 1463-1471, 1996.
37. Cortes Ledesma F, El Khamisy SF, Zuma MC, Osborn K, and Caldecott KW. A human 5¢-tyrosyl DNA phosphodi-esterase that repairs topoisomerase-mediated DNA damage. Nature 461: 674-678, 2009.
38. Darnell G and Richardson DR. The potentialof 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, 1999.
39. Daroui P, Desai SD, Li TK, Liu AA, and Liu LF. Hydrogen peroxide induces topoisomerase I-mediated DNA damage and cell death. J Biol Chem 279: 14587-14594, 2004.
40. 4 coordination unit in a protein. Proc Natl Acad Sci USA 93: 8836-8840, 1996.
41. Davies KJ, Doroshow JH, and Hochstein P. Mitochondrial NADH dehydrogenase-catalyzed oxygen radical production by adriamycin, and the relative inactivity of 5-imino-daunorubicin. FEBS Lett 153: 227-230, 1983.
42. Davies SL, Bergh J, Harris AL, and Hickson ID. Response to ICRF-159 in cell lines resistant to cleavable complex-forming topoisomerase II inhibitors. Br J Cancer 75: 816-821, 1997.
43. Dayani PN, Bishop MC, Black K, and Zeltzer PM. Desfer-oxamine (DFO)-mediated iron chelation: rationale for a novel approach to therapy for brain cancer. J Neurooncol 67: 367-377, 2004.
44. De Domenico I, McVey Ward D, and Kaplan J. Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol 9: 72-81, 2008.
45. De Domenico I, Ward DM, and Kaplan J. Specific iron chelators determine the route of ferritin degradation. Blood 114: 4546-4551, 2009.
46. de Silva DM, Askwith CC, and Kaplan J. Molecular mechanisms of iron uptake in eukaryotes. Physiol Rev 76: 31-47, 1996.
47. Dean RT, Fu S, Stocker R, and Davies MJ. Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 324 (Pt 1): 1-18, 1997.
48. Deweese JE, Burch AM, Burgin AB, and Osheroff N. Use of divalent metal ions in the DNA cleavage reaction of human type II topoisomerases. Biochemistry 48: 1862-1869, 2009.
49. Deweese JE, Burgin AB, and Osheroff N. Human topoi-somerase IIalpha uses a two-metal-ion mechanism for DNA cleavage. Nucleic Acids Res 36: 4883-4893, 2008.
50. Deweese JE, Guengerich FP, Burgin AB, and Osheroff N. Metal ion interactions in the DNA cleavage/ligation active site of human topoisomerase IIalpha. Biochemistry 48: 8940-8947, 2009.
51. Deweese JE and Osheroff N. The use of divalent metal ions by type II topoisomerases. Metallomics 2: 450-459, 2010.
52. Di Leo A, Larsimont D, Gancberg D, Jarvinen T, Beauduin M, Vindevoghel A, Michel J, Focan CH, Ries F, Gobert PH, Closon-Dejardin MT, Dolci S, Rouas G, Paesmans M, Lo-belle JP, Isola J, and Piccart MJ. HER-2 and topo-isomerase IIalpha as predictive markers in a population of node-positive breast cancer patients randomly treated with adjuvant CMF or epirubicin plus cyclophosphamide. Ann Oncol 12: 1081-1089, 2001.
53. Dickey JS and Rao VA. Current and proposed biomarkers of anthracycline cardiotoxicity in cancer: emerging opportunities in oxidative damage and autophagy. Curr Mol Med 12: 763-771, 2012.
54. diTargiani RC, Lee SJ, Wassink S, and Michel SL. Functional characterization of iron-substituted tristetraprolin-2D (TTP-2D, NUP475-2D): RNA binding affinity and selectivity. Biochemistry 45: 13641-13649, 2006.
55. Doroshow JH and Davies KJ. Comparative cardiac oxygen radical metabolism by anthracycline antibiotics, mitoxan-trone, bisantrene, 4¢-(9- acridinylamino)-methanesulfon-m-anisidide, and neocarzinostatin. Biochem Pharmacol 32: 2935-2939, 1983.
56. Doroshow JH and Davies KJ. Redox cycling of anthracy-clines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical. J Biol Chem 261: 3068-3074, 1986.
57. Doroshow JH, Locker GY, and Myers CE. Enzymatic defenses of the mouse heart against reactive oxygen metabolites: alterations produced by doxorubicin. J Clin Invest 65: 128-135, 1980.
58. Doroshow JH, Synold TW, Somlo G, Akman SA, and Ga-jewski E. Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin. Blood 97: 2839-2845, 2001.
59. Downes CS, Clarke DJ, Mullinger AM, Gimenez-Abian JF, Creighton AM, and Johnson RT. A topoisomerase II-dependent G2 cycle checkpoint in mammalian cells. Nature 372: 467-470, 1994.
60. Durrani A. The effect of solvent on stability constant of mixed ligand complexes. Rasayan J Chem 4: 554-556, 2011.
61. Eilers M, Endo T, and Schatz G. Adriamycin, a drug interacting with acidic phospholipids, blocks import of precursor proteins by isolated yeast mitochondria. J Biol Chem 264: 2945-2950, 1989.
62. Elbl L, Hrstkova H, Tomaskova I, and Michalek J. Late anthracycline cardiotoxicity protection by dexrazoxane (ICRF-187) in pediatric patients: echocardiographic follow-up. Support Care Cancer 14: 128-136, 2006.
63. Ewer MS, Von Hoff DD, and Benjamin RS. A historical perspective of anthracycline cardiotoxicity. Heart Fail Clin 7: 363-372, 2011.
64. Fan JR, Peng AL, Chen HC, Lo SC, Huang TH, and Li TK. Cellular processing pathways contribute to the activation of etoposide-induced DNA damage responses. DNA Repair (Amst) 7: 452-463, 2008.
65. Faulk WP, Hsi BL, and Stevens PJ. Transferrin and trans-ferrin receptors in carcinoma of the breast. Lancet 2: 390-392, 1980.
66. Ferrans VJ, Clark JR, Zhang J, Yu ZX, and Herman EH. Pathogenesis and prevention of doxorubicin cardiomyop-athy. Tsitologiia 39: 928-937, 1997.
67. Fu S, Davies MJ, Stocker R, and Dean RT. Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque. Biochem J 333 (Pt 3): 519-525, 1998.
68. Gazak R, Svobodova A, Psotova J, Sedmera P, Prikrylova V, Walterova D, and Kren V. Oxidised derivatives of sily-bin and their antiradical and antioxidant activity. Bioorg Med Chem 12: 5677-5687, 2004.
69. Georgakilas AG and Panayiotidis M. Biomarkers of oxi-dative stress and cancer. from chemistry, biology to clinical applications and personalized therapy. Curr Mol Med 12: 653-654, 2012.
70. Germe T and Hyrien O. Topoisomerase II-DNA complexes trapped by ICRF-193 perturb chromatin structure. EMBO Rep 6: 729-735, 2005.
71. Gervasi PG, Agrillo MR, Lippi A, Bernardini N, Danesi R, and Del Tacca M. Superoxide anion production by doxo-rubicin analogs in heart sarcosomes and by mitochondrial NADH dehydrogenase. Res Commun Chem Pathol Pharmacol 67: 101-115, 1990.
72. Gomez HL, Pinto JA, Olivera M, Vidaurre T, Doimi FD, Vigil CE, Velarde RG, Abugattas JE, Alarcon E, and Val-lejos CS. Topoisomerase II-alpha as a predictive factor of response to therapy with anthracyclines in locally advanced breast cancer. Breast 20: 39-45, 2011.
73. Goodman J and Hochstein P. Generation of free radicals and lipid peroxidation by redox cycling of adriamycin and daunomycin. Biochem Biophys Res Commun 77: 797-803, 1977.
74. Goormaghtigh E, Huart P, Brasseur R, and Ruysschaert JM. Mechanism of inhibition of mitochondrial enzymatic complex I-III by adriamycin derivatives. Biochim Biophys Acta 861: 83-94, 1986.
75. Goormaghtigh E, Huart P, Praet M, Brasseur R, and Ruysschaert JM. Structure of the adriamycin-cardiolipin complex. Role in mitochondrial toxicity. Biophys Chem 35: 247-257, 1990.
76. Grauslund M, Thougaard AV, Fuchtbauer A, Hofland KF, Hjorth PH, Jensen PB, Sehested M, Fuchtbauer EM, and Jensen LH. A mouse model for studying the interaction of bisdioxopiperazines with topoisomerase IIalpha in vivo. Mol Pharmacol 72: 1003-1014, 2007.
77. Halliwell B and Gutteridge JM. Biologically relevant metal ion-dependent hydroxyl radical generation. An update. FEBS Lett 307: 108-112, 1992.
78. Hasinoff BB. Chemistry of dexrazoxane and analogues. Semin Oncol 25: 3-9, 1998.
79. Hasinoff BB, Abram ME, Barnabe N, Khelifa T, Allan WP, and Yalowich JC. The catalytic DNA topoisomerase II inhibitor dexrazoxane (ICRF-187) induces differentiation and apoptosis in human leukemia K562 cells. Mol Pharmacol 59: 453-461, 2001.
80. Hasinoff BB, Hellmann K, Herman EH, and Ferrans VJ. Chemical, biological and clinical aspects of dexrazoxane and other bisdioxopiperazines. Curr Med Chem 5: 1-28, 1998.
81. Hasinoff BB and Herman EH. Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol 7: 140-144, 2007.
82. Hasinoff BB, Kuschak TI, Yalowich JC, and Creighton AM. A QSAR study comparing the cytotoxicity and DNA to-poisomerase II inhibitory effects of bisdioxopiperazine analogs of ICRF-187 (dexrazoxane). Biochem Pharmacol 50: 953-958, 1995.
83. Hasinoff BB and Patel D. The iron chelator Dp44mT does not protect myocytes against doxorubicin. J Inorg Biochem 103: 1093-1101, 2009.
84. Hasinoff BB, Schnabl KL, Marusak RA, Patel D, and Huebner E. Dexrazoxane (ICRF-187) protects cardiac myocytes against doxorubicin by preventing damage to mitochondria. Cardiovasc Toxicol 3: 89-99, 2003.
85. Hasinoff BB and Tran KT. The displacement of iron(III) from its complexes with the anticancer drugs piroxantrone and losoxantrone by the hydrolyzed form of the cardioprotective agent dexrazoxane. J Inorg Biochem 77: 257-259, 1999.
86. Hatcher HC, Singh RN, Torti FM, and Torti SV. Synthetic and natural iron chelators: therapeutic potential and clinical use. Future Med Chem 1: 1643-1670, 2009.
87. Henichart JP, Waring MJ, Riou JF, Denny WA, and Bailly C. Copper-dependent oxidative and topoisomerase II-medi-ated DNA cleavage by a netropsin/4¢-(9-acridinylamino)-methanesulfon-m-anisidide combilexin. Mol Pharmacol 51: 448-461, 1997.
88. Herman EH, el-Hage A, and Ferrans VJ. Protective effect of ICRF-187 on doxorubicin-induced cardiac and renal toxic-ity in spontaneously hypertensive (SHR) and normotensive (WKY) rats. Toxicol Appl Pharmacol 92: 42-53, 1988.
89. Herman EH, el-Hage AN, Creighton AM, Witiak DT, and Ferrans VJ. Comparison of the protective effect of ICRF-187 and structurally related analogues against acute daunoru-bicin toxicity in Syrian golden hamsters. Res Commun Chem Pathol Pharmacol 48: 39-55, 1985.
90. Herman EH and Ferrans VJ. Timing of treatment with ICRF-187 and its effect on chronic doxorubicin cardiotoxi-city. Cancer Chemother Pharmacol 32: 445-449, 1993.
91. Herman EH and Ferrans VJ. Preclinical animal models of cardiac protection from anthracycline-induced cardiotoxi-city. Semin Oncol 25: 15-21, 1998.
92. Herman EH, Ferrans VJ, Young RS, and Hamlin RL. Pre-treatment with ICRF-187 allows a marked increase in the total cumulative dose of doxorubicin tolerated by beagle dogs. Drugs Exp Clin Res 14: 563-570, 1988.
93. Herman EH, Zhang J, Chadwick DP, and Ferrans VJ. Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats. Cancer Chemother Pharmacol 45: 329-334, 2000.
94. Hershko C, Pinson A, and Link G. Prevention of anthra-cycline cardiotoxicity by iron chelation. Acta Haematol 95: 87-92, 1996.
95. Hoke EM, Maylock CA, and Shacter E. Desferal inhibits breast tumor growth and does not interfere with the tu-moricidal activity of doxorubicin. Free Radic Biol Med 39: 403-411, 2005.
96. Huang H, Chen Q, Ku X, Meng L, Lin L, Wang X, Zhu C, Wang Y, Chen Z, Li M, Jiang H, Chen K, Ding J, and Liu H. A series of alpha-heterocyclic carboxaldehyde thiosemi-carbazones inhibit topoisomerase IIalpha catalytic activity. J Med Chem 53: 3048-3064, 2010.
97. Huang KC, Gao H, Yamasaki EF, Grabowski DR, Liu S, Shen LL, Chan KK, Ganapathi R, and Snapka RM. Topoi-somerase II poisoning by ICRF-193. J Biol Chem 276: 44488-44494, 2001.
98. Hutcheson RM, Engelmann MD, and Cheng IF. Voltam-metric studies of Zn and Fe complexes of EDTA: evidence for the push mechanism. Biometals 18: 43-51, 2005.
99. Isaacs RJ, Davies SL, Sandri MI, Redwood C, Wells NJ, and Hickson ID. Physiological regulation of eukaryotic topoi-somerase II. Biochim Biophys Acta 1400: 121-137, 1998.
100. Ishida R, Miki T, Narita T, Yui R, Sato M, Utsumi KR, Tanabe K, and Andoh T. Inhibition of intracellular topoi-somerase II by antitumor bis(2, 6-dioxopiperazine) derivatives: mode of cell growth inhibition distinct from that of cleavable complex-forming type inhibitors. Cancer Res 51: 4909-4916, 1991.
101. Ishida R, Sato M, Narita T, Utsumi KR, Nishimoto T, Morita T, Nagata H, and Andoh T. Inhibition of DNA to-poisomerase II by ICRF-193 induces polyploidization by uncoupling chromosome dynamics from other cell cycle events. J Cell Biol 126: 1341-1351, 1994.
102. Jacobs A. Serum ferritin. Birth Defects Orig Artic Ser 12: 97-103, 1976.
103. Jacobs A. Low molecular weight intracellular iron transport compounds. Blood 50: 433-439, 1977.
104. Jacobs A. Serum ferritin and iron stores. Fed Proc 36: 2024-2027, 1977.
105. Jansson PJ, Hawkins CL, Lovejoy DB, and Richardson DR. The iron complex of Dp44mT is redox-active and induces hydroxyl radical formation: an EPR study. J Inorg Biochem 104: 1224-1228, 2010.
106. Jomova K and Valko M. Advances in metal-induced oxi-dative stress and human disease. Toxicology 283: 65-87, 2011.
107. Joyner JC, Reichfield J, and Cowan JA. Factors influencing the DNA nuclease activity of iron, cobalt, nickel, and copper chelates. J Am Chem Soc 133: 15613-15626, 2011.
108. Kalinowski DS, Quach P, and Richardson DR. Thiosemi-carbazones: the new wave in cancer treatment. Future Med Chem 1: 1143-1151, 2009.
109. Kalyanaraman B. Oxidative chemistry of fluorescent dyes: implications in the detection of reactive oxygen and nitrogen species. Biochem Soc Trans 39: 1221-1225, 2011.
110. Kalyanaraman B, Darley-Usmar V, Davies KJ, Dennery PA, Forman HJ, Grisham MB, Mann GE, Moore K, Roberts LJ, 2nd, and Ischiropoulos H. Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations. Free Radic Biol Med 52: 1-6, 2012.
111. Kanter MM, Hamlin RL, Unverferth DV, Davis HW, and Merola AJ. Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin. J Appl Physiol 59: 1298-1303, 1985.
112. Karlsson M, Kurz T, Brunk UT, Nilsson SE, and Frennesson CI. What does the commonly used DCF test for oxidative stress really show? Biochem J 428: 183-190, 2010.
113. Kaur M, Velmurugan B, Tyagi A, Agarwal C, Singh RP, and Agarwal R. Silibinin suppresses growth of human co-lorectal carcinoma SW480 cells in culture and xenograft through down-regulation of beta-catenin-dependent signaling. Neoplasia 12: 415-424, 2010.
114. Kaur M, Velmurugan B, Tyagi A, Deep G, Katiyar S, Agarwal C, and Agarwal R. Silibinin suppresses growth and induces apoptotic death of human colorectal carcinoma LoVo cells in culture and tumor xenograft. Mol Cancer Ther 8: 2366-2374, 2009.
115. Kennedy LJ, Moore K, Jr., Caulfield JL, Tannenbaum SR, and Dedon PC. Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents. Chem Res Toxicol 10: 386-392, 1997.
116. Kepp O, Galluzzi L, Lipinski M, Yuan J, and Kroemer G. Cell death assays for drug discovery. Nat Rev Drug Discov 10: 221-237, 2011.
117. Kersting G, Tzvetkov MV, Huse K, Kulle B, Hafner V, Brockmoller J, and Wojnowski L. Topoisomerase II beta expression level correlates with doxorubicin-induced apo-ptosis in peripheral blood cells. Naunyn Schmiedebergs Arch Pharmacol 374: 21-30, 2006.
118. Keyer K and Imlay JA. Superoxide accelerates DNA damage by elevating free-iron levels. Proc Natl Acad Sci USA 93: 13635-13640, 1996.
119. Kim R, Hirabayashi N, Nishiyama M, Jinushi K, Toge T, and Okada K. Experimental studies on biochemical modulation targeting topoisomerase I and II in human tumor xenografts in nude mice. Int J Cancer 50: 760-766, 1992.
120. Kinders RJ, Hollingshead M, Lawrence S, Ji J, Tabb B, Bonner WM, Pommier Y, Rubinstein L, Evrard YA, Parchment RE, Tomaszewski J, and Doroshow JH. Development of a validated immunofluorescence assay for gammaH2AX as a pharmacodynamic marker of topoi-somerase I inhibitor activity. Clin Cancer Res 16: 5447-5457, 2010.
121. Klamt F and Shacter E. Taurine chloramine, an oxidant derived from neutrophils, induces apoptosis in human B lymphoma cells through mitochondrial damage. J Biol Chem 280: 21346-21352, 2005.
122. Klayman DL, Bartosevich JF, Griffin TS, Mason CJ, and Scovill JP. 2-Acetylpyridine thiosemicarbazones. 1. A new class of potential antimalarial agents. J Med Chem 22: 855-862, 1979.
123. Klayman DL, Scovill JP, Mason CJ, Bartosevich JF, Bruce J, and Lin AJ. 2-Acetylpyridine thiosemicarbazones. 6.2-Acetylpyridine and 2-butyrylpyridine thiosemicarbazones as antileukemic agents. Arzneimittelforschung 33: 909-912, 1983.
124. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, Baba M, Baehrecke EH, Bahr BA, Ballabio A, Bamber BA, Bassham DC, Bergamini E, Bi X, Biard-Pie-chaczyk M, Blum JS, Bredesen DE, Brodsky JL, Brumell JH, Brunk UT, Bursch W, Camougrand N, Cebollero E, Cecconi F, Chen Y, Chin LS, Choi A, Chu CT, Chung J, Clarke PG, Clark RS, Clarke SG, Clave C, Cleveland JL, Codogno P, Colombo MI, Coto-Montes A, Cregg JM, Cuervo AM, Debnath J, Demarchi F, Dennis PB, Dennis PA, Deretic V, Devenish RJ, Di Sano F, Dice JF, Difiglia M, Dinesh-Kumar S, Distelhorst CW, Djavaheri-Mergny M, Dorsey FC, Droge W, Dron M, Dunn WA, Jr., Duszenko M, Eissa NT, Elazar Z, Esclatine A, Eskelinen EL, Fesus L, Finley KD, Fuentes JM, Fueyo J, Fujisaki K, Galliot B, Gao FB, Gewirtz DA, Gibson SB, Gohla A, Goldberg AL, Gonzalez R, Gonzalez-Estevez C, Gorski S, Gottlieb RA, Haussinger D, He YW, Heidenreich K, Hill JA, Hoyer-Hansen M, Hu X, Huang WP, Iwasaki A, Jaattela M, Jackson WT, Jiang X, Jin S, Jo-hansen T, Jung JU, Kadowaki M, Kang C, Kelekar A, Kessel DH, Kiel JA, Kim HP, Kimchi A, Kinsella TJ, Kiselyov K, Kitamoto K, Knecht E, Komatsu M, Kominami E, Kondo S, Kovacs AL, Kroemer G, Kuan CY, Kumar R, Kundu M, Landry J, Laporte M, Le W, Lei HY, Lenardo MJ, Levine B, Lieberman A, Lim KL, Lin FC, Liou W, Liu LF, Lopez-Berestein G, Lopez-Otin C, Lu B, Macleod KF, Malorni W, Martinet W, Matsuoka K, Mautner J, Meijer AJ, Melendez A, Michels P, Miotto G, Mistiaen WP, Mizushima N, Mo-grabi B, Monastyrska I, Moore MN, Moreira PI, Moriyasu Y, Motyl T, Munz C, Murphy LO, Naqvi NI, Neufeld TP, Nishino I, Nixon RA, Noda T, Nurnberg B, Ogawa M, Oleinick NL, Olsen LJ, Ozpolat B, Paglin S, Palmer GE, Papassideri I, Parkes M, Perlmutter DH, Perry G, Piacentini M, Pinkas-Kramarski R, Prescott M, Proikas-Cezanne T, Raben N, Rami A, Reggiori F, Rohrer B, Rubinsztein DC, Ryan KM, Sadoshima J, Sakagami H, Sakai Y, Sandri M, Sasakawa C, Sass M, Schneider C, Seglen PO, Seleverstov O, Settleman J, Shacka JJ, Shapiro IM, Sibirny A, Silva-Za-carin EC, Simon HU, Simone C, Simonsen A, Smith MA, Spanel-Borowski K, Srinivas V, Steeves M, Stenmark H, Stromhaug PE, Subauste CS, Sugimoto S, Sulzer D, Suzuki T, Swanson MS, Tabas I, Takeshita F, Talbot NJ, Talloczy Z, Tanaka K, Tanaka K, Tanida I, Taylor GS, Taylor JP, Ter-man A, Tettamanti G, Thompson CB, Thumm M, Tolk-ovsky AM, Tooze SA, Truant R, Tumanovska LV, Uchiyama Y, Ueno T, Uzcategui NL, van der Klei I, Va-quero EC, Vellai T, Vogel MW, Wang HG, Webster P, Wiley JW, Xi Z, Xiao G, Yahalom J, Yang JM, Yap G, Yin XM, Yoshimori T, Yu L, Yue Z, Yuzaki M, Zabirnyk O, Zheng X, Zhu X, and Deter RL. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4: 151-175, 2008.
125. Kobayashi S, Volden P, Timm D, Mao K, Xu X, and Liang Q. Transcription factor GATA4 inhibits doxorubicin-induced autophagy and cardiomyocyte death. J Biol Chem 285: 793-804, 2010.
126. Kobayashi T, Guo LL, and Nishida Y. Mechanism of double-strand DNA cleavage effected by iron-bleomycin. Z Naturforsch C 53: 867-870, 1998.
127. Kohn KW and Grimek-Ewig RA. Alkaline elution analysis, a new approach to the study of DNA single-strand interruptions in cells. Cancer Res 33: 1849-1853, 1973.
128. Kohn KW and Pommier Y. Molecular and biological determinants of the cytotoxic actions of camptothecins. Perspective for the development of new topoisomerase I inhibitors. Ann N Y Acad Sci 922: 11-26, 2000.
129. Kohn KW, Shao RG, and Pommier Y. How do drug-induced topoisomerase I-DNA lesions signaltothe molecular interaction network that regulates cell cycle checkpoints, DNA replication, and DNA repair? Cell Biochem Biophys 33: 175-180, 2000.
130. Kondapi AK, Satyanarayana N, and Saikrishna AD. A study of the topoisomerase II activity in HIV-1 replication using the ferrocene derivatives as probes. Arch Biochem Biophys 450: 123-132, 2006.
131. Kovacevic Z, Kalinowski DS, Lovejoy DB, Quach P, Wong J, and Richardson DR. Iron chelators: development of novel compounds with high and selective anti-tumour activity. Curr Drug Deliv 7:194-207, 2010.
132. Kovacevic Z, Kalinowski DS, Lovejoy DB, Yu Y, Suryo Rahmanto Y, Sharpe PC, Bernhardt PV, and Richardson DR. The medicinal chemistry of novel iron chelators for the treatment of cancer. Curr Top Med Chem 11: 483-499, 2011.
133. Kovacs GT, Erlaky H, Toth K, Horvath E, Szabolcs J, Csoka M, Jokuti L, Erdelyi D, and Muller J. Subacute cardiotoxi-city caused by anthracycline therapy in children: can dex-razoxane prevent this effect? Eur J Pediatr 166: 1187-1188, 2007.
134. Kurz T and Brunk UT. Autophagy of HSP70 and chelation of lysosomal iron in a non-redox-active form. Autophagy 5: 93-95, 2009.
135. Kushner BH, Kramer K, and Cheung NK. Oral etoposide for refractory and relapsed neuroblastoma. J Clin Oncol 17: 3221-3225, 1999.
136. Kwan KY and Wang JC. Mice lacking DNA topoisomerase IIIbeta develop to maturity but show a reduced mean lifespan. Proc Natl Acad Sci USA 98: 5717-5721, 2001.
137. Lai HW, Chien SY, Kuo SJ, Tseng LM, Lin HY, Chi CW, and Chen DR. The potential utility of curcumin in the treatment of HER-2-overexpressed breast cancer: an in vitro and in vivo comparison study with herceptin. Evid Based Complement Alternat Med 2012: 486568.
138. Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, and Cole SP. Structural organization of the human TOP2A and TOP2B genes. Gene 221: 255-266, 1998.
139. Larsen AK, Escargueil AE, and Skladanowski A. Catalytic topoisomerase II inhibitors in cancer therapy. Pharmacol Ther 99: 167-181, 2003.
140. Larsen AK, Skladanowski A, and Bojanowski K. The roles of DNA topoisomerase II during the cell cycle. Prog Cell Cycle Res 2: 229-239, 1996.
141. Lebrecht D, Setzer B, Ketelsen UP, Haberstroh J, and Walker UA. Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy. Circulation 108: 2423-2429, 2003.
142. Lebrecht D and Walker UA. Role of mtDNA lesions in anthracycline cardiotoxicity. Cardiovasc Toxicol 7: 108-113, 2007.
143. Lee S, Jung SR, Heo K, Byl JA, Deweese JE, Osheroff N, and Hohng S. DNA cleavage and opening reactions of human topoisomerase IIalpha are regulated via Mg2+-mediated dynamic bending of gate-DNA. Proc Natl Acad Sci USA 109: 2925-2930, 2012.
144. Lefrak EA, Pitha J, Rosenheim S, and Gottlieb JA. A clini-copathologic analysis of adriamycin cardiotoxicity. Cancer 32: 302-314, 1973.
145. Lemasters JJ and Nieminen AL. (Eds). Mitochondria in Pa-thogenesis. New York, NY: Kluwer Academic/Plenum Publishers, 2001.
146. Lesko SA, Lorentzen RJ, and Ts'o PO. Role of superoxide in deoxyribonucleic acid strand scission. Biochemistry 19: 3023-3028, 1980.
147. Levine RL, Wehr N, Williams JA, Stadtman ER, and Shacter E. Determination of carbonyl groups in oxidized proteins. Methods Mol Biol 99: 15-24, 2000.
148. Li TK, Chen AY, Yu C, Mao Y, Wang H, and Liu LF. Activation of topoisomerase II-mediated excision of chromo-somal DNA loops during oxidative stress. Genes Dev 13: 1553-1560, 1999.
149. Li W and Wang JC. Mammalian DNA topoisomerase IIIalpha is essential in early embryogenesis. Proc Natl Acad Sci USA 95: 1010-1013, 1998.
150. Lipshultz SE and Adams MJ. Cardiotoxicity after childhood cancer: beginning with the end in mind. J Clin Oncol 28: 1276-1281, 2010.
151. Lipshultz SE, Cohen H, Colan SD, and Herman EH. The relevance of information generated by in vitro experimental models to clinical doxorubicin cardiotoxicity. Leuk Lym-phoma 47: 1454-1458, 2006.
152. Lipshultz SE, Rifai N, Dalton VM, Levy DE, Silverman LB, Lipsitz SR, Colan SD, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Gelber RD, and Sallan SE. The effect of dexrazoxane on myocar-dial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 351: 145-153, 2004.
153. Lipshultz SE, Scully RE, Lipsitz SR, Sallan SE, Silverman LB, Miller TL, Barry EV, Asselin BL, Athale U, Clavell LA, Larsen E, Moghrabi A, Samson Y, Michon B, Schorin MA, Cohen HJ, Neuberg DS, Orav EJ, and Colan SD. Assessment of dexrazoxane as a cardioprotectant in doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: long-term follow-up of a prospective, randomised, multicentre trial. Lancet Oncol 11: 950-961, 2010.
154. Liu IF, Annamalai T, Sutherland JH, and Tse-Dinh YC. Hydroxyl radicals are involved in cell killing by the bacterial topoisomerase I cleavage complex. J Bacteriol 191: 5315-5319, 2009.
155. Long BH, Wang L, Lorico A, Wang RC, Brattain MG, and Casazza AM. Mechanisms of resistance to etoposide and teniposide in acquired resistant human colon and lung carcinoma cell lines. Cancer Res 51: 5275-5283, 1991.
156. Lovejoy DB, Jansson PJ, Brunk UT, Wong J, Ponka P, and Richardson DR. Antitumor activity of metal-chelating compound Dp44mT is mediated by formation of a redox-active copper complex that accumulates in lysosomes. Cancer Res 71: 5871-5880, 2011.
157. Lovett BD, Lo Nigro L, Rappaport EF, Blair IA, Osheroff N, Zheng N, Megonigal MD, Williams WR, Nowell PC, and Felix CA. Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation. Proc Natl Acad Sci USA 98: 9802-9807, 2001.
158. Lovett BD, Strumberg D, Blair IA, Pang S, Burden DA, Megonigal MD, Rappaport EF, Rebbeck TR, Osheroff N, Pommier YG, and Felix CA. Etoposide metabolites enhance DNA topoisomerase II cleavage near leukemia-associated MLL translocation breakpoints. Biochemistry 40: 1159-1170, 2001.
159. Lu DY, Huang M, Xu CH, Zhu H, Xu B, and Ding J. Medicinal chemistry of probimane and MST-16: comparison of anticancer effects between bisdioxopiperazines. Med Chem 2: 369-375, 2006.
160. Lu DY, Xu B, and Ding J. Antitumor effects of two bis-dioxopiperazines against two experimental lung cancer models in vivo. BMC Pharmacol 4: 32, 2004.
161. Lu J, Wang W, Tan G, Landry AP, Yi P, Si F, Ren Y, and Ding H. Escherichia coli topoisomerase I is an iron and zinc binding protein. Biometals 24: 729-736, 2011.
162. Lukianova OA and David SS. A role for iron-sulfur clusters in DNA repair. Curr Opin Chem Biol 9: 145-151, 2005.
163. Lyu YL, Kerrigan JE, Lin CP, Azarova AM, Tsai YC, Ban Y, and Liu LF. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardio-toxicity and prevention by dexrazoxane. Cancer Res 67: 8839-8846, 2007.
164. Lyu YL, Lin CP, Azarova AM, Cai L, Wang JC, and Liu LF. Role of topoisomerase IIbeta in the expression of develop-mentally regulated genes. Mol Cell Biol 26: 7929-7941, 2006.
165. Lyu YL and Wang JC. Aberrant lamination in the cerebral cortex of mouse embryos lacking DNA topoisomerase II-beta. Proc Natl Acad Sci USA 100: 7123-7128, 2003.
166. Malik M and Nitiss JL. DNA repair functions that control sensitivity to topoisomerase-targeting drugs. Eukaryot Cell 3: 82-90, 2004.
167. Mao Y, Desai SD, Ting CY, Hwang J, and Liu LF. 26 S proteasome-mediated degradation of topoisomerase II cleavable complexes. J Biol Chem 276: 40652-40658, 2001.
168. Martell AE and Smith RM. (Eds). Critical Stability Constants New York: Plenum Press, 1989.
169. Meier B, Scherk C, Schmidt M, and Parak F. pH-dependent inhibition by azide and fluoride of the iron superoxide dismutase from Propionibacterium shermanii. Biochem J 331 (Pt 2): 403-407, 1998.
170. Miller LD, Coffman LG, Chou JW, Black MA, Bergh J, D'Agostino R, Jr., Torti SV, and Torti FM. An iron regulatory gene signature predicts outcome in breast cancer. Cancer Res 71: 6728-6737, 2011.
171. Miller MC, 3rd, Stineman CN, Vance JR, West DX, and Hall IH. The cytotoxicity of copper(II) complexes of 2-acetyl-pyridyl-4N-substituted thiosemicarbazones. Anticancer Res 18: 4131-4139, 1998.
172. Mizushima N and Yoshimori T. How to interpret LC3 immunoblotting. Autophagy 3: 542-545, 2007.
173. Mordente A, Martorana GE, Meucci E, Santini SA, and Littarru GP. Enzyme inactivation by metal-catalyzed oxidation of coenzyme Q1. Biochim Biophys Acta 1100: 235-241, 1992.
174. Mordente A, Miggiano GA, Martorana GE, Meucci E, Santini SA, and Castelli A. Alkaline phosphatase inactiva-tion by mixed function oxidation systems. Arch Biochem Biophys 258: 176-185, 1987.
175. Morgan SE, Cadena RS, Raimondi SC, and Beck WT. Selection of human leukemic CEM cells for resistance to the DNA topoisomerase II catalytic inhibitor ICRF-187 results in increased levels of topoisomerase IIalpha and altered G(2)/M checkpoint and apoptotic responses. Mol Pharmacol 57: 296-307, 2000.
176. Morham SG, Kluckman KD, Voulomanos N, and Smithies O. Targeted disruption of the mouse topoisomerase I gene by camptothecin selection. Mol Cell Biol 16: 6804-6809, 1996.
177. Muller I, Niethammer D, and Bruchelt G. Anthracycline-derived chemotherapeutics in apoptosis and free radical cytotoxicity (Review). Int J Mol Med 1: 491-494, 1998.
178. Munoz IG, Moran JF, Becana M, and Montoya G. The crystal structure of an eukaryotic iron superoxide dis-mutase suggests intersubunit cooperation during catalysis. Protein Sci 14: 387-394, 2005.
179. Murren J, Modiano M, Clairmont C, Lambert P, Savaraj N, Doyle T, and Sznol M. Phase I and pharmacokinetic study of triapine, a potent ribonucleotide reductase inhibitor, administered daily for five days in patients with advanced solid tumors. Clin Cancer Res 9: 4092-4100, 2003.
180. Myers CE, Gianni L, Simone CB, Klecker R, and Greene R. Oxidative destruction of erythrocyte ghost membranes catalyzed by the doxorubicin-iron complex. Biochemistry 21: 1707-1712, 1982.
181. Myers CE, McGuire W, and Young R. Adriamycin: amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep 60: 961-962, 1976.
182. Myers CE, McGuire WP, Liss RH, Ifrim I, Grotzinger K, and Young RC. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. Science 197: 165-167, 1977.
183. Nikolenyi A, Sukosd F, Kaizer L, Csorgo E, Voros A, Uhercsak G, Ormandi K, Lazar G, Thurzo L, Brodowicz T, and Kahan Z. Tumor topoisomerase II alpha status and response to anthracycline-based neoadjuvant chemotherapy in breast cancer. Oncology 80: 269-277, 2011.
184. Nitiss JL. Investigating the biological functions of DNA topoisomerases in eukaryotic cells. Biochim Biophys Acta 1400: 63-81, 1998.
185. Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer 9: 338-350, 2009.
186. Nohl H. Demonstration of the existence of an organo-spe-cific NADH dehydrogenase in heart mitochondria. Eur J Biochem 169: 585-591, 1987.
187. Nohl H. Identification of the site of adriamycin-activation in the heart cell. Biochem Pharmacol 37: 2633-2637, 1988.
188. Noulsri E, Richardson DR, Lerdwana S, Fucharoen S, Yama-gishi T, Kalinowski DS, and Pattanapanyasat K. Antitumor activity and mechanism of action of the iron chelator, Dp44mT, against leukemic cells. Am J Hematol 84: 170-176, 2009.
189. Olive PL. The comet assay. An overview of techniques. Methods Mol Biol 203: 179-194, 2002.
190. Olson RD, Boerth RC, Gerber JG, and Nies AS. Mechanism of adriamycin cardiotoxicity: evidence for oxidative stress. Life Sci 29: 1393-1401, 1981.
191. Omichinski JG, Trainor C, Evans T, Gronenborn AM, Clore GM, and Felsenfeld G. A small single-"finger" peptide from the erythroid transcription factor GATA-1 binds specifically to DNA as a zinc or iron complex. Proc Natl Acad Sci USA 90: 1676-1680, 1993.
192. Ott R and Krämer R. DNA hydrolysis by inorganic catalysts. Appl Microbiol Biotechnol 52: 761-767, 1999.
193. Pedersen-Bjergaard J, Andersen MK, Christiansen DH, and Nerlov C. Genetic pathways in therapy-related myelodys-plasia and acute myeloid leukemia. Blood 99: 1909-1912, 2002.
194. Petering DH, Byrnes RW, and Antholine WE. The role of redox-active metals in the mechanism of action of bleo-mycin. Chem Biol Interact 73: 133-182, 1990.
195. Petering DH, Mao Q, Li W, DeRose E, and Antholine WE. Metallobleomycin-DNA interactions: structures and reactions related to bleomycin-induced DNA damage. Met Ions Biol Syst 33: 619-648, 1996.
196. Pfister TD, Reinhold WC, Agama K, Gupta S, Khin SA, Kinders RJ, Parchment RE, Tomaszewski JE, Doroshow JH, and Pommier Y. Topoisomerase I levels in the NCI-60 cancer cell line panel determined by validated ELISA and microarray analysis and correlation with indenoisoquino-line sensitivity. Mol Cancer Ther 8: 1878-1884, 2009.
197. Pilch DR, Sedelnikova OA, Redon C, Celeste A, Nussenz-weig A, and Bonner WM. Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol 81: 123-129, 2003.
198. Pommier Y. Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints. Curr Med Chem Anticancer Agents 4: 429-434, 2004.
199. Pommier Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 6: 789-802, 2006.
200. Pommier Y, Barcelo JM, Rao VA, Sordet O, Jobson AG, Thibaut L, Miao ZH, Seiler JA, Zhang H, Marchand C, Agama K, Nitiss JL, and Redon C. Repair of topoisomerase I-mediated DNA damage. Prog Nucleic Acid Res Mol Biol 81: 179-229, 2006.
201. Pommier Y, Leo E, Zhang H, and Marchand C. DNA to-poisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol 17: 421-433, 2010.
202. Pommier Y, Tanizawa A, and Kohn KW. Mechanisms of topoisomerase I inhibition by anticancer drugs. Adv Pharmacol 29B: 73-92, 1994.
203. Pouillart P. Evaluating the role of dexrazoxane as a cardi-oprotectant in cancer patients receiving anthracyclines. Cancer Treat Rev 30: 643-650, 2004.
204. Pourquier P, Ueng LM, Fertala J, Wang D, Park HJ, Essig-mann JM, Bjornsti MA, and Pommier Y. Induction of reversible complexes between eukaryotic DNA topoi-somerase I and DNA-containing oxidative base damages. 7, 8-dihydro-8-oxoguanine and 5-hydroxycytosine. J Biol Chem 274: 8516-8523, 1999.
205. Qian H and Yang Y. Alterations of cellular organelles in human liver-derived hepatoma G2 cells induced by adria-mycin. Anticancer Drugs 20: 779-786, 2009.
206. Quiles JL, Huertas JR, Battino M, Mataix J, and Ramirez-Tortosa MC. Antioxidant nutrients and adriamycin toxic-ity. Toxicology 180: 79-95, 2002.
207. Rao VA, Agama K, Holbeck S, and Pommier Y. Batracylin (NSC 320846), a dual inhibitor of DNA topoisomerases I and II induces histone gamma-H2AX as a biomarker of DNA damage. Cancer Res 67: 9971-9979, 2007.
208. Rao VA, Fan AM, Meng L, Doe CF, North PS, Hickson ID, and Pommier Y. Phosphorylation of BLM, dissociation from topoisomerase IIIalpha, and colocalization with gamma-H2AX after topoisomerase I-induced replication damage. Mol Cell Biol 25: 8925-8937, 2005.
209. Rao VA, Klein SR, Agama KK, Toyoda E, Adachi N, Pom-mier Y, and Shacter EB. The iron chelator Dp44mT causes DNA damage and selective inhibition of topoisomerase IIalpha in breast cancer cells. Cancer Res 69: 948-957, 2009.
210. Rao VA, Klein SR, Bonar SJ, Zielonka J, Mizuno N, Dickey JS, Keller PW, Joseph J, Kalyanaraman B, and Shacter E. The antioxidant transcription factor Nrf2 negatively regulates autophagy and growth arrest induced by the anticancer re-dox agent mitoquinone. J Biol Chem 285: 34447-34459, 2010.
211. Rao VA, Zhang J, Klein SR, Espandiari P, Knapton A, Dickey JS, Herman E, and Shacter EB. The iron chelator Dp44mT inhibits the proliferation of cancer cells but fails to protect from doxorubicin-induced cardiotoxicity in spontaneously hypertensive rats. Cancer Chemother Pharmacol 68: 1125-1134, 2011.
212. Ren B, Duan X, and Ding H. Redox control of the DNA damage-inducible protein DinG helicase activity via its iron-sulfur cluster. J Biol Chem 284: 4829-4835, 2009.
213. Requena JR, Fu MX, Ahmed MU, Jenkins AJ, Lyons TJ, Baynes JW, and Thorpe SR. Quantification of mal-ondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipo-protein. Biochem J 322 (Pt 1): 317-325, 1997.
214. Richardson DR. Molecular mechanisms of iron uptake by cells and the use of iron chelators for the treatment of cancer. Curr Med Chem 12: 2711-2729, 2005.
215. Richardson DR, Kalinowski DS, Lau S, Jansson PJ, and Lovejoy DB. Cancer cell iron metabolism and the development of potent iron chelators as anti-tumour agents. Biochim Biophys Acta 1790: 702-717, 2009.
216. Richardson DR and Ponka P. The molecular mechanisms of the metabolism and transport of iron in normal and neo-plastic cells. Biochim Biophys Acta 1331: 1-40, 1997.
217. Richardson J, Thomas KA, Rubin BH, and Richardson DC. Crystal structure of bovine Cu, Zn superoxide dismutase at 3 A resolution: chain tracing and metal ligands. Proc Natl Acad Sci USA 72: 1349-1353, 1975.
218. Robert J. Preclinical assessment of anthracycline cardio-toxicity in laboratory animals: predictiveness and pitfalls. Cell Biol Toxicol 23: 27-37, 2007.
219. Robinson KM, Janes MS, Pehar M, Monette JS, Ross MF, Hagen TM, Murphy MP, and Beckman JS. Selective fluorescent imaging of superoxide in vivo using ethidium-based probes. Proc Natl Acad Sci USA 103: 15038-15043, 2006.
220. Roca J, Ishida R, Berger JM, Andoh T, and Wang JC. An-titumor bisdioxopiperazines inhibit yeast DNA topoi-somerase II by trapping the enzyme in the form of a closed protein clamp. Proc Natl Acad Sci USA 91: 1781-1785, 1994.
221. Rouault TA. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol 2: 406-414, 2006.
222. Rudolf J, Makrantoni V, Ingledew WJ, Stark MJ, and White MF. The DNA repair helicases XPD and FancJ have essential iron-sulfur domains. Mol Cell 23: 801-808, 2006.
223. Sabourin M and Osheroff N. Sensitivity of human type II topoisomerases to DNA damage: stimulation of enzyme-mediated DNA cleavage by abasic, oxidized and alkylated lesions. Nucleic Acids Res 28: 1947-1954, 2000.
224. Saletta F, Rahmanto YS, Siafakas AR, and Richardson DR. Cellular iron depletion and the mechanisms involved in the iron-dependent regulation of the growth arrest and DNA damage family of genes. J Biol Chem 286: 35396-35406, 2011.
225. Sawyer DB, Peng X, Chen B, Pentassuglia L, and Lim CC. Mechanisms of anthracycline cardiac injury: can we identify strategies for cardioprotection? Prog Cardiovasc Dis 53: 105-113, 2010.
226. Schindlbeck C, Mayr D, Olivier C, Rack B, Engelstaedter V, Jueckstock J, Jenderek C, Andergassen U, Jeschke U, and Friese K. Topoisomerase IIalpha expression rather than gene amplification predicts responsiveness of adjuvant anthracycline-based chemotherapy in women with primary breast cancer. J Cancer Res Clin Oncol 136: 1029-1037, 2010.
227. Schmidt BH, Burgin AB, Deweese JE, Osheroff N, and Berger JM. A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases. Nature 465: 641-644, 2010.
228. Schneider E, Horton JK, Yang CH, Nakagawa M, and Cowan KH. Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoi-somerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance. Cancer Res 54: 152-158, 1994.
229. Schneider YJ, Baurain R, Zenebergh A, and Trouet A. DNA-binding parameters of daunorubicin and doxorubicin in the conditions used for studying the interaction of an-thracycline-DNA complexes with cells in vitro. Cancer Chemother Pharmacol 2: 7-10, 1979.
230. Seifried HE, McDonald SS, Anderson DE, Greenwald P, and Milner JA. The antioxidant conundrum in cancer. Cancer Res 63: 4295-4298, 2003.
231. Shacter E, Williams JA, Lim M, Levine RL. Differential susceptibility of plasma proteins to oxidative modification: examination by western blot immunoassay. Free Radic Biol Med 17: 429-437, 1994.
232. Shires TK. Iron-induced DNA damage and synthesis in isolated rat liver nuclei. Biochem J 205: 321-329, 1982.
233. Shterman N, Kupfer B, and Moroz C. Comparison of transferrin receptors, iron content and isoferritin profile in normal and malignant human breast cell lines. Pathobiology 59: 19-25, 1991.
234. Shukla S, Srivastava RS, Shrivastava SK, Sodhi A, and Kumar P. Synthesis, characterization and antiproliferative activity of 1, 2-naphthoquinone and its derivatives. Appl Biochem Biotechnol 167: 1430-1435, 2012.
235. Simonart T, Boelaert JR, Andrei G, Clercq ED, and Snoeck R. Iron withdrawal strategies fail to prevent the growth of SiHa-induced tumors in mice. Gynecol Oncol 90: 91-95, 2003.
236. Simonart T, Boelaert JR, Andrei G, van den Oord JJ, De-graef C, Hermans P, Noel JC, Van Vooren JP, Heenen M, De Clercq E, and Snoeck R. Desferrioxamine enhances AIDS-associated Kaposi's sarcoma tumor development in a xenograft model. Int J Cancer 100: 140-143, 2002.
237. Simunek T, Sterba M, Popelova O, Adamcova M, Hrdina R, and Gersl V. Anthracycline-induced cardiotoxicity: overview of studies examining the roles of oxidative stress and free cellular iron. Pharmacol Rep 61: 154-171, 2009.
238. Sinha BK, Mimnaugh EG, Rajagopalan S, and Myers CE. Adriamycin activation and oxygen free radical formation in human breast tumor cells: protective role of glutathione peroxidase in adriamycin resistance. Cancer Res 49: 3844-3848, 1989.
239. Sissi C and Palumbo M. Effects of magnesium and related divalent metal ions in topoisomerase structure and function. Nucleic Acids Res 37: 702-711, 2009.
240. Smith PJ. Ferrous iron-mediated enhancement of DNA damage and recovery potential in bleomycin-treated human cells. Biochem Pharmacol 36: 475-480, 1987.
241. Sng JH, Heaton VJ, Bell M, Maini P, Austin CA, and Fisher LM. Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for iso-form evolution through gene duplication. Biochim Biophys Acta 1444: 395-406, 1999.
242. Sordet O, Khan QA, Kohn KW, and Pommier Y. Apoptosis induced by topoisomerase inhibitors. Curr Med Chem An-ticancer Agents 3: 271-290, 2003.
243. Sordet O, Khan QA, Plo I, Pourquier P, Urasaki Y, Yoshida A, Antony S, Kohlhagen G, Solary E, Saparbaev M, Laval J, and Pommier Y. Apoptotic topoisomerase I-DNA complexes induced by staurosporine-mediated oxygen radicals. J Biol Chem 279: 50499-50504, 2004.
244. Spagnuolo RD, Recalcati S, Tacchini L, and Cairo G. Role of hypoxia-inducible factors in the dexrazoxane-mediated protection of cardiomyocytes from doxorubicin-induced toxicity. Br J Pharmacol 163: 299-312, 2011.
245. Spickett CM, Wiswedel I, Siems W, Zarkovic K, and Zar-kovic N. Advances in methods for the determination of biologically relevant lipid peroxidation products. Free Radic Res 44: 1172-1202, 2010.
246. Stadtman ER. Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med 9: 315-325, 1990.
247. Subramanian D, Furbee CS, and Muller MT. ICE bioassay. Isolating in vivo complexes of enzyme to DNA. Methods Mol Biol 95: 137-147, 2001.
248. Swain SM, Whaley FS, Gerber MC, Weisberg S, York M, Spicer D, Jones SE, Wadler S, Desai A, Vogel C, Speyer J, Mittelman A, Reddy S, Pendergrass K, Velez-Garcia E, Ewer MS, Bianchine JR, and Gams RA. Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer. J Clin Oncol 15: 1318-1332, 1997.
249. Synold TW, Tetef ML, and Doroshow JH. Antineoplastic activity of continuous exposure to dexrazoxane: potential new role as a novel topoisomerase II inhibitor. Semin Oncol 25: 93-99, 1998.
250. Tan C, Tasaka H, Yu KP, Murphy ML, and Karnofsky DA. Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia. Cancer 20: 333-353, 1967.
251. Tanabe K, Ikegami Y, Ishida R, and Andoh T. Inhibition of topoisomerase II by antitumor agents bis(2, 6-dioxopiper-azine) derivatives. Cancer Res 51: 4903-4908, 1991.
252. Tanida I, Minematsu-Ikeguchi N, Ueno T, and Kominami E. Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy 1: 84-91, 2005.
253. Tanigawa N, Katoh H, Kan N, Mizuno Y, Tanimura H, Satomura K, and Hikasa Y. Effect of vitamin E on toxicity and antitumor activity of adriamycin in mice. Jpn J Cancer Res 77: 1249-1255, 1986.
254. Tennyson RB and Lindsley JE. Type II DNA topoisomerase from Saccharomyces cerevisiae is a stable dimer. Biochemistry 36: 6107-6114, 1997.
255. Tetef ML, Synold TW, Chow W, Leong L, Margolin K, Morgan R, Raschko J, Shibata S, Somlo G, Yen Y, Groshen S, Johnson K, Lenz HJ, Gandara D, and Doroshow JH. Phase I trial of 96-hour continuous infusion of dexrazoxane in patients with advanced malignancies. Clin Cancer Res 7: 1569-1576, 2001.
256. Thelander L and Graslund A. Mechanism of inhibition of mammalian ribonucleotide reductase by the iron chelate of 1-formylisoquinoline thiosemicarbazone. Destruction of the tyrosine free radical of the enzyme in an oxygen-requiring reaction. J Biol Chem 258: 4063-4066, 1983.
257. Thongphasuk P, Stremmel W, and Chamulitrat W. 2, 3-Dehydrosilybin is a better DNA topoisomerase I inhibitor than its parental silybin. Chemotherapy 55: 42-48, 2009.
258. Tian J, Peehl DM, Zheng W, and Knox SJ. Anti-tumor and radiosensitization activities of the iron chelator HDp44mT are mediated by effects on intracellular redox status. Cancer Lett 298: 231-237, 2010.
259. Toyokuni S and Sagripanti JL. Iron-mediated DNA damage: sensitive detection of DNA strand breakage catalyzed by iron. J Inorg Biochem 47: 241-248, 1992.
260. Traore HN and Meyer D. Necrosis of host cells and survival of pathogens following iron overload in an in vitro model of co-infection with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis. Int J Antimicrob Agents 29: 465-470, 2007.
261. Tukenova M, Guibout C, Oberlin O, Doyon F, Mousannif A, Haddy N, Guerin S, Pacquement H, Aouba A, Hawkins M, Winter D, Bourhis J, Lefkopoulos D, Diallo I, and de Vathaire F. Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J Clin Oncol 28: 1308-1315, 2010.
262. Tutem E, Apak R, and Sozgen K. The interaction of anti-tumor-active anthraquinones with biologically important redox couples: I. Spectrophotometric investigation of the interaction of carminic acid and mitoxantrone with the iron (II, III) and copper (I, II) redox couples. J Inorg Biochem 61: 79-96, 1996.
263. Valko M, Morris H, and Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 12: 1161-1208, 2005.
264. Valko M, Rhodes CJ, Moncol J, Izakovic M, and Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160: 1-40, 2006.
265. van Hille B, Etievant C, Barret JM, Kruczynski A, and Hill BT. Characterization of the biological and biochemical activities of F 11782 and the bisdioxopiperazines, ICRF-187 and ICRF-193, two types of topoisomerase II catalytic inhibitors with distinctive mechanisms of action. Anticancer Drugs 11: 829-841, 2000.
266. Vassal G, Pondarre C, Cappelli C, Terrier-Lacombe MJ, Boland I, Morizet J, Benard J, Venuat AM, Ardouin P, Hartmann O, and Gouyette A. DNA-topoisomerase I, a new target for the treatment of neuroblastoma. Eur J Cancer 33: 2011-2015, 1997.
267. Velez JM, Miriyala S, Nithipongvanitch R, Noel T, Plab-plueng CD, Oberley T, Jungsuwadee P, Van Remmen H, Vore M, and St. Clair DK. p53 regulates oxidative stress-mediated retrograde signaling: a novel mechanism for chemotherapy-induced cardiac injury. PLoS One 6: e18005, 2011.
268. Venable RO, Saba CF, Endicott MM, and Northrup NC. Dexrazoxane treatment of doxorubicin extravasation injury in four dogs. J Am Vet Med Assoc 240: 304-307, 2012.
269. Voest EE, van Acker SA, van der Vijgh WJ, van Asbeck BS, and Bast A. Comparison of different iron chelators as protective agents against acute doxorubicin-induced car-diotoxicity. J Mol Cell Cardiol 26: 1179-1185, 1994.
270. Von Hoff DD. Phase I trials of dexrazoxane and other potential applications for the agent. Semin Oncol 25: 31-36, 1998.
271. Von Hoff DD and Layard M. Risk factors for development of daunorubicin cardiotoxicity. Cancer Treat Rep 65 Suppl 4: 19-23, 1981.
272. Von Hoff DD, Layard M, Rozencweig M, and Muggia FM. Time relationship between last dose of daunorubicin and congestive heart failure. Cancer Treat Rep 61: 1411-1413, 1977.
273. Von Hoff DD, Layard MW, Basa P, Davis HL, Jr., Von Hoff AL, Rozencweig M, and Muggia FM. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91: 710-717, 1979.
274. Von Hoff DD, Rozencweig M, Layard M, Slavik M, and Muggia FM. Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases. Am J Med 62: 200-208, 1977.
275. Wadler S, Green MD, Basch R, and Muggia FM. Lethal and sublethal effects of the combination of doxorubicin and the bisdioxopiperazine, (+)-1, 2,-bis (3-5-dioxopiperazinyl-1-yl) propane (ICRF 187), on murine sarcoma S180 in vitro. Bio-chem Pharmacol 36: 1495-1501, 1987.
276. Wadler S, Green MD, and Muggia FM. Synergistic activity of doxorubicin and the bisdioxopiperazine (+)-1, 2-bis(3, 5-dioxopiperazinyl-1-yl)propane (ICRF 187) against the mu-rine sarcoma S180 cell line. Cancer Res 46: 1176-1181, 1986.
277. Wang JC. DNA topoisomerases: from a laboratory curiosity to a subject in cancer chemotherapy. NCI Monogr 3-6, 1987.
278. Wang JC. DNA topoisomerases as targets of therapeutics: an overview. Adv Pharmacol 29A: 1-19, 1994.
279. Wang JC. DNA topoisomerases. Annu Rev Biochem 65: 635-692, 1996.
280. Wang JC. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3: 430-440, 2002.
281. Wang L and Eastmond DA. Catalytic inhibitors of topoi-somerase II are DNA-damaging agents: induction of chromosomal damage by merbarone and ICRF-187. Environ Mol Mutagen 39: 348-356, 2002.
282. Wattanapitayakul SK, Chularojmontri L, Herunsalee A, Charuchongkolwongse S, Niumsakul S, and Bauer JA. Screening of antioxidants from medicinal plants for cardi-oprotective effect against doxorubicin toxicity. Basic Clin Pharmacol Toxicol 96: 80-87, 2005.
283. Webb MR and Ebeler SE. Comparative analysis of topoi-somerase IB inhibition and DNA intercalation by flavo-noids and similar compounds: structural determinates of activity. Biochem J 384: 527-541, 2004.
284. Wei L, Easmon J, Nagi RK, Muegge BD, Meyer LA, and Lewis JS. 64Cu-azabicyclo[3.2.2]nonane thiosemicarbazone complexes: radiopharmaceuticals for PET of topoisomerase II expression in tumors. J Nucl Med 47: 2034-2041, 2006.
285. Wessel I, Jensen LH, Jensen PB, Falck J, Rose A, Roerth M, Nitiss JL, and Sehested M. Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187 demonstrate a functional R162Q mutation in the Walker A consensus ATP binding domain of the alpha isoform. Cancer Res 59: 3442-3450, 1999.
286. Whitnall M, Howard J, Ponka P, and Richardson DR. A class of iron chelators with a wide spectrum of potent an-titumor activity that overcomes resistance to chemothera-peutics. Proc Natl Acad Sci USA 103: 14901-14906, 2006.
287. Whitnall M, Suryo Rahmanto Y, Sutak R, Xu X, Becker EM, Mikhael MR, Ponka P, and Richardson DR. The MCK mouse heart model of Friedreich's ataxia: alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation. Proc Natl Acad Sci USA 105: 9757-9762, 2008.
288. Xiang P, Deng HY, Li K, Huang GY, Chen Y, Tu L, Ng PC, Pong NH, Zhao H, Zhang L, and Sung RY. Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model. Cancer Chemother Pharmacol 63: 343-349, 2009.
289. Xu X, Chen K, Kobayashi S, Timm D, and Liang Q. Re-sveratrol attenuates doxorubicin-induced cardiomyocyte death via inhibition of S6k1-mediated autophagy. J Pharmacol Exp Ther 341: 183-195, 2012.
290. Xu X, Persson HL, and Richardson DR. Molecular pharmacology of the interaction of anthracyclines with iron. Mol Pharmacol 68: 261-271, 2005.
291. Xu X, Sutak R, and Richardson DR. Iron chelation by clinically relevant anthracyclines: alteration in expression of iron-regulated genes and atypical changes in intracellular iron distribution and trafficking. Mol Pharmacol 73: 833-844, 2008.
292. Yalowich JC, Wu X, Zhang R, Kanagasabai R, Hornbaker M, and Hasinoff BB. The anticancer thiosemicarbazones Dp44mT and triapine lack inhibitory effects as catalytic inhibitors or poisons of DNA topoisomerase IIalpha. Bio-chem Pharmacol 84: 52-58, 2012.
293. Yan T, Deng S, Metzger A, Godtel-Armbrust U, Porter AC, and Wojnowski L. Topoisomerase II{alpha}-dependent and-independent apoptotic effects of dexrazoxane and doxo-rubicin. Mol Cancer Ther 8: 1075-1085, 2009.
294. Yanauchi O and Odani A. Stability constants of metal complexes of amino acids with charges side chains-Part I: positive charged side chains. Pure Appl Chem 68: 469-496, 1996.
295. Yang DC, Wang F, Elliott RL, and Head JF. Expression of transferrin receptor and ferritin H-chain mRNA are associated with clinical and histopathological prognostic indicators in breast cancer. Anticancer Res 21: 541-549, 2001.
296. Yu Y, Kovacevic Z, and Richardson DR. Tuning cell cycle regulation with an iron key. Cell Cycle 6: 1982-1994, 2007.
297. Yuan J, Lovejoy DB, and Richardson DR. Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment. Blood 104: 1450-1458, 2004.
298. Zamocky M and Koller F. Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis. Prog Biophys Mol Biol 72: 19-66, 1999.
299. Zeng Z, Cortes-Ledesma F, El Khamisy SF, and Caldecott KW. TDP2/TTRAP is the major 5¢-tyrosyl DNA phospho-diesterase activity in vertebrate cells and is critical for cellular resistance to topoisomerase II-induced DNA damage. J Biol Chem 286: 403-409, 2011.
300. Zhang A, Lyu YL, Lin CP, Zhou N, Azarova AM, Wood LM, and Liu LF. A protease pathway for the repair of to-poisomerase II-DNA covalent complexes. J Biol Chem 281: 35997-36003, 2006.
301. Zhou L, Sung RY, Li K, Pong NH, Xiang P, Shen J, Ng PC, and Chen Y. Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: anti-apoptosis and promoting angiogenesis. Int J Cardiol 152: 196-201, 2011.
302. Zhou Y, Hileman EO, Plunkett W, Keating MJ, and Huang P. Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anti-cancer agents. Blood 101: 4098-4104, 2003.
303. Zielonka J, Hardy M, and Kalyanaraman B. HPLC study of oxidation products of hydroethidine in chemical and biological systems: ramifications in superoxide measurements. Free Radic Biol Med 46: 329-338, 2009.
304. Zielonka J and Kalyanaraman B. Hydroethidine-and Mi-toSOX-derived red fluorescence is not a reliable indicator of intracellular superoxide formation: another inconvenient truth. Free Radic Biol Med 48: 983-1001, 2010.
305. Zielonka J, Srinivasan S, Hardy M, Ouari O, Lopez M, Vasquez-Vivar J, Avadhani NG, and Kalyanaraman B. Cytochrome c-mediated oxidation of hydroethidine and mito-hydroethidine in mitochondria: identification of homo-and heterodimers. Free Radic Biol Med 44: 835-846, 2008.
306. Zielonka J, Vasquez-Vivar J, and Kalyanaraman B. Detection of 2-hydroxyethidium in cellular systems: a unique marker product of superoxide and hydroethidine. Nat Protoc 3: 8-21, 2008.
307. Zunino F, Di Marco A, Zaccara A, and Gambetta RA. The interaction of daunorubicin and doxorubicin with DNA and chromatin. Biochim Biophys Acta 607: 206-214, 1980.
308. Zuo L and Clanton TL. Detection of reactive oxygen and nitrogen species in tissues using redox-sensitive fluorescent probes. Methods Enzymol 352: 307-325, 2002.