The iron chelator Dp44mT causes DNA damage and selective inhibition of topoisomerase IIA in breast cancer cells

Cancer Research

Volumn 69, Issue 3, 2009, Pages 948-957

  Rao, V Ashutosh ^a,b,e   Klein, Sarah R ^a   Agama, Keli K ^c   Toyoda, Eriko ^d   Adachi, Noritaka ^d   Pommier, Yves ^c   Shacter, Emily B ^a,e  

^a U S DEPARTMENT OF HEALTH AND HUMAN SERVICES   (United States)

^b Food and Drug Administration   (Japan)

^c NATIONAL CANCER INSTITUTE   (United States)

^d YOKOHAMA CITY UNIVERSITY   (Japan)

^e NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHECKPOINT KINASE 1; CHECKPOINT KINASE 2; DEFEROXAMINE MESYLATE; DI 2 PYRIDYLKETONE 4,4 DIMETHYL 3 THIOSEMICARBAZONE; DNA TOPOISOMERASE (ATP HYDROLYSING); DOXORUBICIN; HISTONE H2AX; IRON CHELATING AGENT; RAZOXANE; SMALL INTERFERING RNA; TOPOISOMERASE 2ALPHA; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER CELL CULTURE; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL KILLING; CONTROLLED STUDY; DNA CLEAVAGE; DNA DAMAGE; DOUBLE STRANDED DNA BREAK; DRUG CYTOTOXICITY; DRUG INHIBITION; DRUG MECHANISM; DRUG POTENTIATION; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; HELA CELL; HUMAN; HUMAN CELL; LEUKEMIA CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION;

ANTIGENS, NEOPLASM; BREAST NEOPLASMS; CELL CYCLE; CELL GROWTH PROCESSES; CELL LINE, TUMOR; DNA DAMAGE; DNA TOPOISOMERASES, TYPE II, EUKARYOTIC; DNA-BINDING PROTEINS; HUMANS; IRON CHELATING AGENTS; THIOSEMICARBAZONES;

EID: 59149089078     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-08-1437     Document Type: Article

References (50)

1. Barry E, Alvarez JA, Scully RE, Miller TL, Lipshultz SE. Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Expert Opin Pharmacother 2007;8:1039-58.
2. Bernhardt PV. Coordination chemistry and biology of chelators for the treatment of iron overload disorders. Dalton Trans 2007;30:3214-20.
3. De Domenico I, McVey Ward D, Kaplan J. Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol 2008;9:72-81.
4. Rouault TA. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol 2006;2:406-14.
5. 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.
6. 1 phase of the cell cycle. Cancer Res 1993;53:3968-75.
7. Yu Y, Kovacevic Z, Richardson DR. Tuning cell cycle regulation with an iron key. Cell Cycle 2007;6:1982-94.
8. 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.
9. Sargent PJ, Farnaud S, Evans RW. Structure/function overview of proteins involved in iron storage and transport. Curr Med Chem 2005;12:2683-93.
10. Faulk WP, Hsi BL, Stevens PJ. Transferrin and transferrin receptors in carcinoma of the breast. Lancet 1980;2:390-2.
11. 2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation. Blood 2005;106:3191-9.
12. 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 U S A 2006;103:14901-6.
13. Lovejoy DB, Richardson DR. Novel "hybrid" iron chelators derived from aroylhydrazones and thiosemicarbazones demonstrate selective antiproliferative activity against tumor cells. Blood 2002;100:666-76.
14. Hoke EM, Maylock CA, Shacter E. Desferal inhibits breast tumor growth and does not interfere with the tumoricidal activity of doxorubicin. Free Radic Biol Med 2005;39:403-11.
15. Hasinoff BB, Herman EH. Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol 2007;7:140-4.
16. Hasinoff BB, Kuschak TI, Yalowich JC, Creighton AM. A QSAR study comparing the cytotoxicity and DNA topoisomerase II inhibitory effects of bisdioxopiperazine analogs of ICRF-187 (dexrazoxane). Biochem Pharmacol 1995;50:953-8.
17. Imondi AR. Preclinical models of cardiac protection and testing for effects of dexrazoxane on doxorubicin antitumor effects. Semin Oncol 1998;25:22-30.
18. Selig RA, White L, Gramacho C, et al. Failure of iron chelators to reduce tumor growth in human neuroblastoma xenografts. Cancer Res 1998;58:473-8.
19. Finch RA, Liu M, Grill SP, et al. Triapine (3-aminopyridine-2- carboxaldehyde-thiosemicarbazone): a potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity. Biochem Pharmacol 2000;59:983-91.
20. Buss JL, Greene BT, Turner J, Torti FM, Torti SV. Iron chelators in cancer chemotherapy. Curr Top Med Chem 2004;4:1623-35.
21. 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.
22. Rao VA, Fan AM, Meng L, et al. Phosphorylation of BLM, dissociation from topoisomerase IIIa, and colocalization with γ-H2AX after topoisomerase I-induced replication damage. Mol Cell Biol 2005;25:8925-37.
23. Pilch DR, Sedelnikova OA, Redon C, et al. Characteristics of γ-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol 2003;81:123-9.
24. Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 2003;3:155-68.
25. Takemura H, Rao VA, Sordet O, et al. Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double strand breaks. J Biol Chem 2006;281:30814-23.
26. Toyoda E, Kagaya S, Cowell IG, et al. NK314, a topoisomerase II inhibitor that specifically targets the α isoform. J Biol Chem 2008;283:23711-20.
27. Rao VA, Agama K, Holbeck S, Pommier Y. Batracylin (NSC 320846), a dual inhibitor of DNA topoisomerases I and II induces histone γ-H2AX as a biomarker of DNA damage. Cancer Res 2007;67:9971-9.
28. Rao VA, Conti C, Guirouilh-Barbat J, et al. Endogenous γ-H2AX-ATM-Chk2 checkpoint activation in Bloom's syndrome helicase deficient cells is related to DNA replication arrested forks. Mol Cancer Res 2007;5:713-24.
29. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988;175:184-91.
30. Olive PL, Banath JP, Durand RE. Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay. Radiat Res 1990;122:86-94.
31. Bartek J, Iggo R, Gannon J, Lane DP. Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. Oncogene 1990;5:893-9.
32. Pommier Y. Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 2006;6:789-802.
33. Champoux JJ. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 2001;70:369-413.
34. Akimitsu N, Adachi N, Hirai H, et al. Enforced cytokinesis without complete nuclear division in embryonic cells depleting the activity of DNA topoisomerase IIα. Genes Cells 2003;8:393-402.
35. Sordet O, Khan QA, Plo I, et al. Apoptotic topoisomerase I-DNA complexes induced by staurosporine-mediated oxygen radicals. J Biol Chem 2004;279:50499-504.
36. Ma B, Goh BC, Tan EH, et al. A multicenter phase II trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) and gemcitabine in advanced non-small-cell lung cancer with pharmacokinetic evaluation using peripheral blood mononuclear cells. Invest New Drugs 2008;26:169-73.
37. Attia S, Kolesar J, Mahoney MR, et al. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas. Invest New Drugs 2008;26:369-79.
38. Hofland KF, Thougaard AV, Dejligbjerg M, et al. Combining etoposide and dexrazoxane synergizes with radiotherapy and improves survival in mice with central nervous system tumors. Clin Cancer Res 2005;11:6722-9.
39. Lyu YL, Kerrigan JE, Lin CP, et al. Topoisomerase IIβ mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res 2007;67:8839-46.
40. Hajji N, Pastor N, Mateos S, Dominguez I, Cortes F. DNA strand breaks induced by the anti-topoisomerase II bis-dioxopiperazine ICRF-193. Mutat Res 2003;530:35-46.
41. Hasinoff BB, Abram ME, Barnabe N, et al. The catalytic DNA topoisomerase II inhibitor dexrazoxane (ICRF-187) induces differentiation and apoptosis in human leukemia K562 cells. Mol Pharmacol 2001;59:453-61.
42. 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.
43. Wang JC. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 2002;3:430-40.
44. Azarova AM, Lyu YL, Lin CP, et al. Roles of DNA topoisomerase II isozymes in chemotherapy and secondary malignancies. Proc Natl Acad Sci U S A 2007;104:11014-9.
45. 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.
46. Capranico G, Tinelli S, Austin CA, Fisher ML, Zunino F. Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta 1992;1132:43-8.
47. Szuts D, Krude T. Cell cycle arrest at the initiation step of human chromosomal DNA replication causes DNA damage. J Cell Sci 2004;117:4897-908.
48. Harper JW, Elledge SJ. The DNA damage response: ten years after. Mol Cell 2007;28:739-45.
49. Fu D, Richardson DR. Iron chelation and regulation of the cell cycle: 2 mechanisms of posttranscriptional regulation of the universal cyclin-dependent kinase inhibitor p21CIP1/WAF1 by iron depletion. Blood 2007;110:752-61.
50. 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.