CoChat
Sign Up
Cited by 62

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Desferal inhibits breast tumor growth and does not interfere with the tumoricidal activity of doxorubicin

Hoke, Eileen M., Maylock, Caroline A., Shacter, Emily·2005·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2005.03.029
Open this paper in CoChat — free account

Abstract

Desferal is a clinically approved iron chelator used to treat iron overload. Doxorubicin is an anthracycline cancer chemotherapy drug used in the treatment of breast cancer. It can undergo redox cycling in the presence of iron to produce reactive oxygen species. The oxidant-generating activity of doxorubicin is thought to be responsible for the cardiotoxic side effects of the drug, but it is unclear whether it is also required for its anti-tumor activity. To test whether an iron-chelating antioxidant would interfere with the tumor-killing activity of doxorubicin, nude mice were transplanted with xenografts of human breast cancer MDA-MB 231 cells and then treated with doxorubicin and/or desferal. Not only did desferal not interfere with the anti-tumor activity of doxorubicin, it inhibited tumor growth on its own. In vitro studies confirmed that desferal inhibits breast tumor growth. However, it did not induce apoptosis, nor did it induce cell cycle arrest. Instead, desferal caused cytostasis, apparently through iron depletion. The cytostatic activity of desferal was partially ameliorated by pretreatment with iron-saturated transferrin, and transferrin receptor expression on breast cancer cells nearly doubled after exposure to desferal. In contrast to its effect on tumor cells, desferal did not inhibit growth of normal breast epithelial cells. The data indicate that the anti-tumor activity of doxorubicin is not dependent on iron-mediated ROS production. Furthermore, desferal ma…

Overview

Integrity signals

Registry

Crossref · 10.1016/j.freeradbiomed.2005.03.029

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Research works printed but not linked: 57

  1. Hortobagyi, 1995, Current status of adjuvant systemic therapy for primary breast cancer: progress and controversy, CA J. Cancer, Clin., 45, 199
  2. Jensen, 2002, Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients, Ann. Oncol., 13, 699, 10.1093/annonc/mdf132 · DOI
  3. Green, 1990, Evidence of the selective alteration of anthracycline activity due to modulation by ICRF-187 (ADR-529), Pharmacol. Ther., 48, 61, 10.1016/0163-7258(90)90018-W · DOI
  4. Singal, 1998, Doxorubicin-induced cardiomyopathy, N. Engl. J. Med., 339, 900, 10.1056/NEJM199809243391307 · DOI
  5. Wiseman, 1998, Dexrazoxane: a review of its use as a cardioprotective agent in patients receiving anthracycline-based chemotherapy, Drugs, 56, 385, 10.2165/00003495-199856030-00009 · DOI
  6. Powis, 1989, Free radical formation by antitumor quinones, Free Radic. Biol. Med., 6, 63, 10.1016/0891-5849(89)90162-7 · DOI
  7. Hershko, 1994, Control of disease by selective iron depletion: a novel therapeutic strategy utilizing iron chelators, Bailliere's Clin. Haematol., 7, 965, 10.1016/S0950-3536(05)80133-7 · DOI
  8. Gewirtz, 1999, A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin, Biochem. Pharmacol., 57, 727, 10.1016/S0006-2952(98)00307-4 · DOI
  9. Minotti, 1999, Role of iron in anthracycline cardiotoxicity: new tunes for an old song?, FASEB J., 13, 199, 10.1096/fasebj.13.2.199 · DOI
  10. al–Harbi, 1992, Prevention of doxorubicin-induced myocardial and haematological toxicities in rats by the iron chelator desferrioxamine, Cancer Chemother. Pharmacol., 31, 200, 10.1007/BF00685548 · DOI
  11. Voest, 1994, Comparison of different iron chelators as protective agents against acute doxorubicin-induced cardiotoxicity, J. Mol. Cell. Cardiol., 26, 1179, 10.1006/jmcc.1994.1136 · DOI
  12. van Acker, 1997, Monohydroxyethylrutoside, a dose-dependent cardioprotective agent, does not affect the antitumor activity of doxorubicin, Clin. Cancer Res., 3, 1747
  13. Saad, 2001, The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats, Pharmacol. Res., 43, 211, 10.1006/phrs.2000.0769 · DOI
  14. Barnabe, 2002, Deferiprone protects against doxorubicin-induced myocyte cytotoxicity, Free Radic. Biol. Med., 33, 266, 10.1016/S0891-5849(02)00873-0 · DOI
  15. Wang, 2004, Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms: intermediacy of H2O2- and p53-dependent pathways, J. Biol. Chem., 279, 25535, 10.1074/jbc.M400944200 · DOI
  16. Halliwell, 1989, Protection against tissue damage in vivo by desferrioxamine: what is its mechanism of action?, Free Radic. Biol. Med., 7, 645, 10.1016/0891-5849(89)90145-7 · DOI
  17. Pahl, 2001, Desferri-exochelin induces death by apoptosis in human breast cancer cells but does not kill normal breast cells, Breast Cancer Res. Treat., 69, 69, 10.1023/A:1012211828319 · DOI
  18. Lee, 1999, Oxidative stress inhibits apoptosis in human lymphoma cells, J. Biol. Chem., 274, 19792, 10.1074/jbc.274.28.19792 · DOI
  19. Anderson, 2002, Oxidative stress inhibits the phagocytosis of apoptotic cells that have externalized phosphatidylserine, Cell Death Differ., 9, 616, 10.1038/sj.cdd.4401013 · DOI
  20. Englert, 2002, Distinct modes of cell death induced by different reactive oxygen species: amino acyl chloramines mediate hypochlorous acid-induced apoptosis, J. Biol. Chem., 277, 20518, 10.1074/jbc.M200212200 · DOI
  21. Ovejera, 1981, Human tumor xenografts in athymic nude mice as a preclinical screen for anticancer agents, Semin. Oncol., 8, 386
  22. Boven, 1992, Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study, Cancer Res., 52, 5940
  23. Mosmann, 1983, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J. Immunol. Methods, 65, 55, 10.1016/0022-1759(83)90303-4 · DOI · Paper page
  24. Su, 2002, Changes in BRCA1 and BRCA2 expression produced by chemotherapeutic agents in human breast cancer cells, Int. J. Biochem. Cell. Biol., 34, 950, 10.1016/S1357-2725(02)00016-X · DOI
  25. Tong, 2002, Iron deficiency can upregulate expression of transferrin receptor at both the mRNA and protein level, Br. J. Haematol., 116, 458, 10.1046/j.1365-2141.2002.03289.x · DOI
  26. Minotti, 2001, Doxorubicin irreversibly inactivates iron regulatory proteins 1 and 2 in cardiomyocytes: evidence for distinct metabolic pathways and implications for iron-mediated cardiotoxicity of antitumor therapy, Cancer Res.61, 8422
  27. Kotamraju, 2000, Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen: role of reactive oxygen and nitrogen species, J. Biol. Chem., 275, 33585, 10.1074/jbc.M003890200 · DOI
  28. Kalyanaraman, 2002, Doxorubicin-induced apoptosis: implications in cardiotoxicity, Mol. Cell. Biochem., 234–235, 119, 10.1023/A:1015976430790 · DOI
  29. Muller, 1997, Effect of concentration on the cytotoxic mechanism of doxorubicin—Apoptosis and oxidative DNA damage, Biochem. Biophys. Res. Commun., 230, 254, 10.1006/bbrc.1996.5898 · DOI
  30. Doroshow, 1986, Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones, Proc. Natl. Acad. Sci. USA, 83, 4514, 10.1073/pnas.83.12.4514 · DOI
  31. Minotti, 2004, Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity, Pharmacol. Rev., 56, 185, 10.1124/pr.56.2.6 · DOI
  32. Senturker, 2002, Induction of apoptosis by chemotherapeutic drugs without generation of reactive oxygen species, Arch. Biochem. Biophys., 397, 262, 10.1006/abbi.2001.2681 · DOI
  33. Shacter, 2000, Oxidative stress interferes with cancer chemotherapy: inhibition of lymphoma cell apoptosis and phagocytosis, Blood, 96, 307, 10.1182/blood.V96.1.307 · DOI
  34. Anderson, 2003, Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells, Nat. Immunol., 4, 87, 10.1038/ni871 · DOI
  35. Conklin, 2000, Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects, Nutr. Cancer, 37, 1, 10.1207/S15327914NC3701_1 · DOI
  36. Speyer, 1988, Protective effect of the bispiperazinedione ICRF–187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer, N. Engl. J. Med., 319, 745, 10.1056/NEJM198809223191203 · DOI
  37. Speyer, 1992, ICRF–187 permits longer treatment with doxorubicin in women with breast cancer, J. Clin. Oncol., 10, 117, 10.1200/JCO.1992.10.1.117 · DOI
  38. Hellmann, 1998, Overview and historical development of dexrazoxane, Semin. Oncol., 25, 48
  39. Swain, 1998, Adult multicenter trials using dexrazoxane to protect against cardiac toxicity, Semin. Oncol., 25, 43
  40. Hensley, 1999, American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants, J. Clin. Oncol., 17, 3333, 10.1200/JCO.1999.17.10.3333 · DOI
  41. Imondi, 1998, Preclinical models of cardiac protection and testing for effects of dexrazoxane on doxorubicin antitumor effects, Semin. Oncol., 25, 22
  42. Summers, 1979, Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects, Br. J. Haematol., 42, 547, 10.1111/j.1365-2141.1979.tb01167.x · DOI
  43. Valle, 1995, Effect of different exposures to desferrioxamine on neuroblastoma cell lines, Pediatr. Hematol. Oncol., 12, 439, 10.3109/08880019509009473 · DOI
  44. Hasinoff, 2001, The catalytic DNA topoisomerase ii inhibitor dexrazoxane (ICRF-187) induces differentiation and apoptosis in human leukemia K562 cells, Mol. Pharmacol., 59, 453, 10.1016/S0026-895X(24)12235-3 · DOI
  45. Finch, 1999, Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP): an inhibitor of ribonucleotide reductase with antineoplastic activity, Adv. Enzyme Regul., 39, 3, 10.1016/S0065-2571(98)00017-X · DOI
  46. Hoffbrand, 1976, Effect of iron deficiency and desferrioxamine on DNA synthesis in human cells, Br. J. Haematol., 33, 517, 10.1111/j.1365-2141.1976.tb03570.x · DOI
  47. Lederman, 1984, Deferoxamine: a reversible S-phase inhibitor of human lymphocyte proliferation, Blood, 64, 748, 10.1182/blood.V64.3.748.748 · DOI
  48. Oblender, 1990, Effects of iron, copper and zinc on the activity of ribonucleotide reductase in normal and leukemic human lymphocytes, Anticancer Res., 10, 123
  49. Furukawa, 1992, Iron deprivation decreases ribonucleotide reductase activity and DNA synthesis, Life Sci., 50, 2059, 10.1016/0024-3205(92)90572-7 · DOI
  50. Cooper, 1996, The relationship of intracellular iron chelation to the inhibition and regeneration of human ribonucleotide reductase, J. Biol. Chem., 271, 20291, 10.1074/jbc.271.34.20291 · DOI
  51. Tilbrook, 1998, Iron chelators for clinical use, Met. Ions Biol. Syst., 35, 691
  52. Buss, 2003, The role of iron chelation in cancer therapy, Curr. Med. Chem., 10, 1021, 10.2174/0929867033457638 · DOI
  53. Brodie, 1993, Neuroblastoma sensitivity to growth inhibition by deferrioxamine: evidence for a block in G1 phase of the cell cycle, Cancer Res., 53, 3968
  54. Donfrancesco, 1990, Effects of a single course of deferoxamine in neuroblastoma patients, Cancer Res., 50, 4929
  55. Dreicer, 1997, A phase II trial of deferoxamine in patients with hormone-refractory metastatic prostate cancer, Cancer Invest., 15, 311, 10.3109/07357909709039731 · DOI
  56. Simonart, 2003, Iron withdrawal strategies fail to prevent the growth of siha-induced tumors in mice, Gynecol. Oncol., 90, 91, 10.1016/S0090-8258(03)00226-9 · DOI
  57. Blatt, 1994, Deferoxamine in children with recurrent neuroblastoma, Anticancer Res., 14, 2109

Cited by

Sorted by citations

See all 62

Metadata

Authors
Hoke, E. M., Maylock, C. A., & Shacter, E.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2005-08
Volume
39
Issue
3
Pages
403-411
ISSN
0891-5849
DOI
10.1016/j.freeradbiomed.2005.03.029
Cited by
62
References
1
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review