Home LiteratureArticle Details
PMID: 19478820 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

Nature reviews. Drug discovery ·Vol. 8 ·No. 7 ·2009-07-00 ·Pages 579-91

Trachootham D, Alexandre J, Huang P

Abstract

Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacological ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.

MeSH Terms
Adaptation, Physiological Animals Drug Resistance, Neoplasm Glutathione/metabolism Humans Neoplasms/drug therapy,metabolism Neoplastic Stem Cells/metabolism Oxidation-Reduction Reactive Oxygen Species/metabolism
Chemicals
Reactive Oxygen Species Glutathione
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Trachootham Dunyaporn
Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Alexandre Jerome
Huang Peng
References (162)
162 references, click to expand
  1. Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence.
    Nat Cell Biol. 2006 Nov;8(11):1291-7 PMID: 17028578
  2. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells.
    Nature. 2004 Oct 21;431(7011):997-1002 PMID: 15496926
  3. Mechanism of synergy of N-(4-hydroxyphenyl)retinamide and ABT-737 in acute lymphoblastic leukemia cell lines: Mcl-1 inactivation.
    J Natl Cancer Inst. 2008 Apr 16;100(8):580-95 PMID: 18398104
  4. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response.
    Nature. 2006 Dec 7;444(7120):756-60 PMID: 17051156
  5. Evidence of ROS generation by mitochondria in cells with impaired electron transport chain and mitochondrial DNA damage.
    Mitochondrion. 2007 Feb-Apr;7(1-2):106-18 PMID: 17307400
  6. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple.
    Free Radic Biol Med. 2001 Jun 1;30(11):1191-212 PMID: 11368918
  7. Effective killing of Gleevec-resistant CML cells with T315I mutation by a natural compound PEITC through redox-mediated mechanism.
    Leukemia. 2008 Jun;22(6):1191-9 PMID: 18385754
  8. Phase I trial of imexon in patients with advanced malignancy.
    J Clin Oncol. 2007 May 1;25(13):1779-84 PMID: 17470869
  9. Mitochondrial mutations in cancer.
    Oncogene. 2006 Aug 7;25(34):4647-62 PMID: 16892079
  10. Involvement of glutathione metabolism in the cytotoxicity of the phenethyl isothiocyanate and its cysteine conjugate to human leukaemia cells in vitro.
    Biochem Pharmacol. 2001 Jan 15;61(2):165-77 PMID: 11163331
  11. Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol gamma.
    EMBO J. 2005 Oct 5;24(19):3482-92 PMID: 16163384
  12. Superoxide dismutase 1 (SOD1) is essential for H2O2-mediated oxidation and inactivation of phosphatases in growth factor signaling.
    Proc Natl Acad Sci U S A. 2008 May 20;105(20):7147-52 PMID: 18480265
  13. Role of p53 in sensing oxidative DNA damage in response to reactive oxygen species-generating agents.
    Cancer Res. 2004 Sep 1;64(17):6233-9 PMID: 15342409
  14. Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients.
    Blood. 1999 Nov 15;94(10):3315-24 PMID: 10552940
  15. Role of mitochondrial DNA in toxic responses to oxidative stress.
    DNA Repair (Amst). 2006 Feb 3;5(2):145-52 PMID: 15878696
  16. Regulation of reactive oxygen species, DNA damage, and c-Myc function by peroxiredoxin 1.
    Oncogene. 2005 Dec 1;24(54):8038-50 PMID: 16170382
  17. Mitochondrial manganese-superoxide dismutase expression in ovarian cancer: role in cell proliferation and response to oxidative stress.
    J Biol Chem. 2005 Nov 25;280(47):39485-92 PMID: 16179351
  18. Sublethal oxidative stress inhibits tumor cell adhesion and enhances experimental metastasis of murine mammary carcinoma.
    Clin Exp Metastasis. 1995 Jan;13(1):16-22 PMID: 7820952
  19. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide.
    N Engl J Med. 1998 Nov 5;339(19):1341-8 PMID: 9801394
  20. Drug discovery: playing dirty.
    Nature. 2005 Oct 13;437(7061):942-3 PMID: 16222266
  21. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.
    N Engl J Med. 2006 Dec 7;355(23):2408-17 PMID: 17151364
  22. Cancer drugs. Smart weapons prove tough to design.
    Science. 2002 Oct 18;298(5593):522-5 PMID: 12386312
  23. Adaptation of energy metabolism in breast cancer brain metastases.
    Cancer Res. 2007 Feb 15;67(4):1472-86 PMID: 17308085
  24. Induction of oxidative stress and apoptosis in myeloma cells by the aziridine-containing agent imexon.
    Biochem Pharmacol. 2000 Sep 15;60(6):749-58 PMID: 10930529
  25. The role of p53 in base excision repair following genotoxic stress.
    Carcinogenesis. 2004 Jan;25(1):11-9 PMID: 14555612
  26. The mitochondrial genome in human adaptive radiation and disease: on the road to therapeutics and performance enhancement.
    Gene. 2005 Jul 18;354:169-80 PMID: 16024186
  27. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis.
    Science. 2008 May 2;320(5876):661-4 PMID: 18388260
  28. An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by beta-lapachone.
    Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11832-7 PMID: 17609380
  29. Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma.
    Clin Cancer Res. 2002 Dec;8(12):3658-68 PMID: 12473574
  30. Regulation of reactive oxygen species and genomic stability in hematopoietic stem cells.
    Antioxid Redox Signal. 2008 Nov;10(11):1883-94 PMID: 18627347
  31. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche.
    Blood. 2007 Oct 15;110(8):3056-63 PMID: 17595331
  32. p53 in health and disease.
    Nat Rev Mol Cell Biol. 2007 Apr;8(4):275-83 PMID: 17380161
  33. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation.
    J Natl Cancer Inst. 2006 Dec 20;98(24):1777-85 PMID: 17179479
  34. Linking stress-signaling, glutathione metabolism, signaling pathways and xenobiotic transporters.
    Cancer Metastasis Rev. 2007 Mar;26(1):59-69 PMID: 17260165
  35. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients.
    J Clin Oncol. 2005 Aug 20;23(24):5805-13 PMID: 16027437
  36. Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase system in the human stomach.
    Free Radic Biol Med. 2007 Dec 15;43(12):1627-38 PMID: 18037128
  37. Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8).
    Blood. 2007 Dec 15;110(13):4436-44 PMID: 17785584
  38. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy.
    J Natl Cancer Inst. 2008 May 7;100(9):672-9 PMID: 18445819
  39. Gene expressions associated with chemosensitivity in human hepatoma cells.
    Hepatogastroenterology. 2007 Mar;54(74):489-92 PMID: 17523305
  40. Effective elimination of fludarabine-resistant CLL cells by PEITC through a redox-mediated mechanism.
    Blood. 2008 Sep 1;112(5):1912-22 PMID: 18574029
  41. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts.
    Science. 1997 Mar 14;275(5306):1649-52 PMID: 9054359
  42. Tumor intracellular redox status and drug resistance--serendipity or a causal relationship?
    Curr Pharm Des. 2004;10(16):1969-77 PMID: 15180532
  43. Chemotherapy: induction of stress responses.
    Endocr Relat Cancer. 2006 Dec;13 Suppl 1:S115-24 PMID: 17259552
  44. Transferrin receptor-dependent iron uptake is responsible for doxorubicin-mediated apoptosis in endothelial cells: role of oxidant-induced iron signaling in apoptosis.
    J Biol Chem. 2002 May 10;277(19):17179-87 PMID: 11856741
  45. Mitochondrial DNA mutations in primary leukemia cells after chemotherapy: clinical significance and therapeutic implications.
    Leukemia. 2003 Aug;17(8):1437-47 PMID: 12886229
  46. Improvement of the therapeutic index of anticancer drugs by the superoxide dismutase mimic mangafodipir.
    J Natl Cancer Inst. 2006 Feb 15;98(4):236-44 PMID: 16478742
  47. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis.
    J Clin Oncol. 2008 Jun 10;26(17):2839-45 PMID: 18539962
  48. Characterization of molecular events in a series of bladder urothelial carcinoma cell lines with progressive resistance to arsenic trioxide.
    Anticancer Drugs. 2004 Sep;15(8):779-85 PMID: 15494640
  49. Cell cycle regulation by oncogenic tyrosine kinases in myeloid neoplasias: from molecular redox mechanisms to health implications.
    Antioxid Redox Signal. 2008 Oct;10(10):1813-48 PMID: 18593226
  50. Sustained phosphorylation of Bid is a marker for resistance to Fas-induced apoptosis during chronic liver diseases.
    Gastroenterology. 2006 Jan;130(1):104-19 PMID: 16401474
  51. The role of oxygen availability in embryonic development and stem cell function.
    Nat Rev Mol Cell Biol. 2008 Apr;9(4):285-96 PMID: 18285802
  52. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress.
    Cell. 2007 Jan 26;128(2):325-39 PMID: 17254970
  53. Experimental therapeutics: targeting the redox Achilles heel of cancer.
    Curr Opin Investig Drugs. 2007 Dec;8(12):1022-37 PMID: 18058573
  54. Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine.
    Cell Death Differ. 2004 Jul;11(7):737-46 PMID: 15002036
  55. Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells.
    Gene. 2004 Aug 4;337:1-13 PMID: 15276197
  56. The signaling mechanism of ROS in tumor progression.
    Cancer Metastasis Rev. 2006 Dec;25(4):695-705 PMID: 17160708
  57. The redox state of the lung cancer microenvironment depends on the levels of thioredoxin expressed by tumor cells and affects tumor progression and response to prooxidants.
    Int J Cancer. 2008 Oct 15;123(8):1770-8 PMID: 18661523
  58. p53 and its isoforms in cancer.
    Br J Cancer. 2007 Aug 6;97(3):277-82 PMID: 17637683
  59. The role of glutathione-S-transferase in anti-cancer drug resistance.
    Oncogene. 2003 Oct 20;22(47):7369-75 PMID: 14576844
  60. Sensor/effector drug design with potential relevance to cancer.
    Curr Pharm Des. 2006;12(34):4479-99 PMID: 17168755
  61. Acquired tolerance of hepatocellular carcinoma cells to selenium deficiency: a selective survival mechanism?
    Cancer Res. 2003 Oct 15;63(20):6707-15 PMID: 14583465
  62. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability.
    Nature. 2005 Jul 7;436(7047):123-7 PMID: 16001073
  63. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis.
    JAMA. 2007 Feb 28;297(8):842-57 PMID: 17327526
  64. Resistance to oxidants associated with elevated catalase activity in HL-60 leukemia cells that overexpress multidrug-resistance protein does not contribute to the resistance to daunorubicin manifested by these cells.
    Cancer Chemother Pharmacol. 1995;35(5):377-86 PMID: 7850918
  65. The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation.
    Mol Cancer Ther. 2003 Mar;2(3):235-43 PMID: 12657718
  66. The antioxidant paradox.
    Lancet. 2000 Apr 1;355(9210):1179-80 PMID: 10791396
  67. Chemosensitization of cancer by nitric oxide.
    Curr Pharm Des. 2008;14(11):1113-23 PMID: 18473858
  68. Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies.
    APMIS. 2007 Feb;115(2):81-103 PMID: 17295675
  69. Activation of antioxidant pathways in ras-mediated oncogenic transformation of human surface ovarian epithelial cells revealed by functional proteomics and mass spectrometry.
    Cancer Res. 2004 Jul 1;64(13):4577-84 PMID: 15231669
  70. Determination of glutathione, glutathione reductase, glutathione peroxidase and glutathione S-transferase levels in human lung cancer tissues.
    Cancer Lett. 1997 Oct 28;119(1):13-9 PMID: 18372516
  71. Superoxide dismutase as a target for the selective killing of cancer cells.
    Nature. 2000 Sep 21;407(6802):390-5 PMID: 11014196
  72. Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin.
    Biochemistry. 1997 Sep 23;36(38):11293-7 PMID: 9333325
  73. c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53 function: a mechanism for oncogene-induced genetic instability.
    Mol Cell. 2002 May;9(5):1031-44 PMID: 12049739
  74. ROS stress in cancer cells and therapeutic implications.
    Drug Resist Updat. 2004 Apr;7(2):97-110 PMID: 15158766
  75. Adaptation to oxidative stress: quinone-mediated protection of signaling in rat lung epithelial L2 cells.
    Biochem Pharmacol. 1997 Apr 4;53(7):987-93 PMID: 9174112
  76. Reactive oxygen species in cancer cells: live by the sword, die by the sword.
    Cancer Cell. 2006 Sep;10(3):175-6 PMID: 16959608
  77. Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism.
    J Biol Chem. 2003 Sep 26;278(39):37832-9 PMID: 12853461
  78. Triapine (3-aminopyridine-2-carboxaldehyde- thiosemicarbazone): A potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity.
    Biochem Pharmacol. 2000 Apr 15;59(8):983-91 PMID: 10692563
  79. NQO1-activated phenothiazinium redox cyclers for the targeted bioreductive induction of cancer cell apoptosis.
    Free Radic Biol Med. 2007 Jul 15;43(2):178-90 PMID: 17603928
  80. Enhanced skin carcinogenesis in transgenic mice with high expression of glutathione peroxidase or both glutathione peroxidase and superoxide dismutase.
    Cancer Res. 1997 Apr 15;57(8):1468-74 PMID: 9108447
  81. Oxidant stress and B vitamins status in patients with non-small cell lung cancer.
    Nutr Cancer. 2007;59(1):8-13 PMID: 17927496
  82. Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents.
    Blood. 2003 May 15;101(10):4098-104 PMID: 12531810
  83. Drug approval triggers debate on future direction for cancer treatments.
    Nat Rev Drug Discov. 2006 Feb;5(2):91 PMID: 16521324
  84. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life.
    Oncogene. 2005 Jan 13;24(3):367-80 PMID: 15531919
  85. Antioxidant enzyme activities and the production of MDA and 8-oxo-dG in chronic lymphocytic leukemia.
    Free Radic Biol Med. 2001 Jun 1;30(11):1286-92 PMID: 11368926
  86. Requirement for Rac1 in a K-ras induced lung cancer in the mouse.
    Cancer Res. 2007 Sep 1;67(17):8089-94 PMID: 17804720
  87. Novel aspects of oxidative stress-associated carcinogenesis.
    Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1373-7 PMID: 16910784
  88. Coping with stress: multiple ways to activate p53.
    Oncogene. 2007 Feb 26;26(9):1306-16 PMID: 17322916
  89. Reactive oxygen species in tumor metastasis.
    Cancer Lett. 2008 Jul 18;266(1):53-9 PMID: 18362051
  90. Lipid peroxidation, free radical production and antioxidant status in breast cancer.
    Breast Cancer Res Treat. 2000 Jan;59(2):163-70 PMID: 10817351
  91. Destructive cycles: the role of genomic instability and adaptation in carcinogenesis.
    Carcinogenesis. 2004 Nov;25(11):2033-44 PMID: 15180945
  92. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions.
    Nat Rev Cancer. 2008 Oct;8(10):755-68 PMID: 18784658
  93. Antioxidants block proteasome inhibitor function in endometrial carcinoma cells.
    Anticancer Drugs. 2008 Feb;19(2):115-24 PMID: 18176107
  94. Reactive oxygen species in oncogenic transformation.
    Biochem Soc Trans. 2003 Dec;31(Pt 6):1441-4 PMID: 14641084
  95. Redox active disulfides: the thioredoxin system as a drug target.
    Oncol Res. 1997;9(6-7):351-6 PMID: 9406241
  96. Motexafin gadolinium: a novel redox active drug for cancer therapy.
    Semin Cancer Biol. 2006 Dec;16(6):466-76 PMID: 17112739
  97. A threshold concept for cancer therapy.
    Med Hypotheses. 2000 Jul;55(1):29-35 PMID: 11021322
  98. Redox regulation of cell survival.
    Antioxid Redox Signal. 2008 Aug;10(8):1343-74 PMID: 18522489
  99. The p53-induced gene-6 (proline oxidase) mediates apoptosis through a calcineurin-dependent pathway.
    J Biol Chem. 2005 Aug 12;280(32):29346-54 PMID: 15914462
  100. Antioxidant status and lipid peroxidation in colorectal cancer.
    J Toxicol Environ Health A. 2001 Oct 12;64(3):213-22 PMID: 11594700
  101. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response.
    Science. 1977 Jul 8;197(4299):165-7 PMID: 877547
  102. Mechanisms of ROS modulated cell survival during carcinogenesis.
    Cancer Lett. 2008 Jul 18;266(1):30-6 PMID: 18372105
  103. Enhancement of chemotherapeutic response of tumor cells by a heme oxygenase inhibitor, pegylated zinc protoporphyrin.
    Int J Cancer. 2004 Mar;109(1):1-8 PMID: 14735461
  104. Models of reactive oxygen species in cancer.
    Drug Discov Today Dis Models. 2007;4(2):67-73 PMID: 18591999
  105. Probing p53 biological functions through the use of genetically engineered mouse models.
    Mutat Res. 2005 Aug 25;576(1-2):4-21 PMID: 16038709
  106. Reactive oxygen species may have antitumor activity in metastatic melanoma.
    J Natl Cancer Inst. 2008 Jan 2;100(1):11-2 PMID: 18159075
  107. Reactive oxygen species: a breath of life or death?
    Clin Cancer Res. 2007 Feb 1;13(3):789-94 PMID: 17289868
  108. Repression of sestrin family genes contributes to oncogenic Ras-induced reactive oxygen species up-regulation and genetic instability.
    Cancer Res. 2007 May 15;67(10):4671-8 PMID: 17510393
  109. Oxidative stress, redox, and the tumor microenvironment.
    Semin Radiat Oncol. 2004 Jul;14(3):259-66 PMID: 15254869
  110. Thioredoxin and thioredoxin-binding protein-2 in cancer and metabolic syndrome.
    Free Radic Biol Med. 2007 Sep 15;43(6):861-8 PMID: 17697931
  111. Adaptive response to GSH depletion and resistance to L-buthionine-(S,R)-sulfoximine: involvement of Nrf2 activation.
    Mol Cell Biochem. 2008 Nov;318(1-2):23-31 PMID: 18587629
  112. 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 Apr;26(2):169-73 PMID: 17851637
  113. Lipid peroxidation, total antioxidant status, and total thiol levels predict overall survival in patients with oral squamous cell carcinoma.
    Integr Cancer Ther. 2007 Dec;6(4):365-72 PMID: 18048884
  114. Role of superoxide dismutase in cancer: a review.
    Cancer Res. 1979 Apr;39(4):1141-9 PMID: 217531
  115. c-Myc phosphorylation is required for cellular response to oxidative stress.
    Mol Cell. 2006 Feb 17;21(4):509-19 PMID: 16483932
  116. Oxidative stress and cancer: have we moved forward?
    Biochem J. 2007 Jan 1;401(1):1-11 PMID: 17150040
  117. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas.
    Invest New Drugs. 2008 Aug;26(4):369-79 PMID: 18278438
  118. Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis.
    Cell. 2005 Jul 29;122(2):221-33 PMID: 16051147
  119. Association of reactive oxygen species levels and radioresistance in cancer stem cells.
    Nature. 2009 Apr 9;458(7239):780-3 PMID: 19194462
  120. The x(c)- cystine/glutamate antiporter: a potential target for therapy of cancer and other diseases.
    J Cell Physiol. 2008 Jun;215(3):593-602 PMID: 18181196
  121. Cellular redox status regulates hypoxia inducible factor-1 activity. Role in tumour development.
    J Exp Clin Cancer Res. 2007 Mar;26(1):39-50 PMID: 17550131
  122. Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo.
    Br J Haematol. 2005 Mar;128(5):636-44 PMID: 15725085
  123. Inflammation and lung cancer: roles of reactive oxygen/nitrogen species.
    J Toxicol Environ Health B Crit Rev. 2008 Jan;11(1):1-15 PMID: 18176884
  124. Copper binding by tetrathiomolybdate attenuates angiogenesis and tumor cell proliferation through the inhibition of superoxide dismutase 1.
    Clin Cancer Res. 2006 Aug 15;12(16):4974-82 PMID: 16914587
  125. Inhibiting catalase activity sensitizes 36B10 rat glioma cells to oxidative stress.
    Free Radic Biol Med. 2007 Mar 15;42(6):787-97 PMID: 17320761
  126. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype.
    Cancer Res. 2008 Mar 15;68(6):1777-85 PMID: 18339858
  127. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  128. Protection from oxidative stress by enhanced glycolysis; a possible mechanism of cellular immortalization.
    Histol Histopathol. 2007 Jan;22(1):85-90 PMID: 17128414
  129. Cancer cell killing via ROS: to increase or decrease, that is the question.
    Cancer Biol Ther. 2008 Dec;7(12):1875-84 PMID: 18981733
  130. Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide.
    Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12288-93 PMID: 17640917
  131. Antioxidant inhibitors for cancer therapy.
    Med Hypotheses. 1998 Nov;51(5):405-9 PMID: 9848469
  132. Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine).
    J Biol Chem. 1979 Aug 25;254(16):7558-60 PMID: 38242
  133. Oxidative stress and apoptosis: a new treatment paradigm in cancer.
    Front Biosci. 2006 Jan 01;11:300-12 PMID: 16146732
  134. NADPH oxidase 1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression.
    Oncogene. 2008 Aug 7;27(34):4724-32 PMID: 18454179
  135. Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo.
    Int J Cancer. 2006 Jul 1;119(1):41-8 PMID: 16450384
  136. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate.
    Cancer Cell. 2006 Sep;10(3):241-52 PMID: 16959615
  137. Expression and activity of NOX5 in the circulating malignant B cells of hairy cell leukemia.
    J Immunol. 2005 Dec 15;175(12):8424-30 PMID: 16339585
  138. Redox regulation by intrinsic species and extrinsic nutrients in normal and cancer cells.
    Annu Rev Nutr. 2005;25:261-95 PMID: 16011468
  139. Antioxidant potential in esophageal, stomach and colorectal cancers.
    Hepatogastroenterology. 2003 Jan-Feb;50(49):126-31 PMID: 12630007
  140. Persistent oxidative stress in cancer.
    FEBS Lett. 1995 Jan 16;358(1):1-3 PMID: 7821417
  141. Resistance to paclitaxel is proportional to cellular total antioxidant capacity.
    Cancer Res. 2005 Sep 15;65(18):8455-60 PMID: 16166325
  142. Aberrant expression of selenoproteins in the progression of colorectal cancer.
    Cancer Lett. 2008 Feb 8;259(2):218-30 PMID: 18054426
  143. Lipid peroxidation and antioxidant status in colorectal cancer.
    World J Gastroenterol. 2005 Jan 21;11(3):403-6 PMID: 15637754
  144. The antioxidant function of the p53 tumor suppressor.
    Nat Med. 2005 Dec;11(12):1306-13 PMID: 16286925
  145. Antioxidant enzyme levels in cancer.
    Histol Histopathol. 1997 Apr;12(2):525-35 PMID: 9151141
  146. Bioenergetics and the formation of mitochondrial reactive oxygen species.
    Trends Pharmacol Sci. 2006 Dec;27(12):639-45 PMID: 17056127
  147. Production of large amounts of hydrogen peroxide by human tumor cells.
    Cancer Res. 1991 Feb 1;51(3):794-8 PMID: 1846317
  148. Drug development of MET inhibitors: targeting oncogene addiction and expedience.
    Nat Rev Drug Discov. 2008 Jun;7(6):504-16 PMID: 18511928
  149. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor.
    Cancer Res. 2007 Nov 15;67(22):10823-30 PMID: 18006827
  150. Increased level of the p67phox subunit of NADPH oxidase by 4HPR in head and neck squamous carcinoma cells.
    Int J Oncol. 2005 Sep;27(3):787-90 PMID: 16077929
  151. Redox regulation and its emerging roles in stem cells and stem-like cancer cells.
    Antioxid Redox Signal. 2009 May;11(5):1107-22 PMID: 18999985
  152. Free radical increases in cancer: evidence that there is not a real increase.
    Science. 1977 Dec 2;198(4320):936-8 PMID: 201025
  153. Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis.
    Biol Chem. 2006 Apr;387(4):365-72 PMID: 16606333
  154. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy.
    Cancer Lett. 2008 Jul 18;266(1):37-52 PMID: 18406051
  155. How important is oxidative damage? Lessons from Alzheimer's disease.
    Free Radic Biol Med. 2000 Mar 1;28(5):831-4 PMID: 10754280
  156. 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 Oct 3;103(40):14901-6 PMID: 17003122
  157. ROS as a tumour suppressor?
    Nat Cell Biol. 2006 Nov;8(11):1213-5 PMID: 17077852
  158. Elesclomol induces cancer cell apoptosis through oxidative stress.
    Mol Cancer Ther. 2008 Aug;7(8):2319-27 PMID: 18723479
  159. The role of macrophage-derived TNFa in the induction of sublethal tumor cell DNA damage.
    Carcinogenesis. 1992 Jan;13(1):77-81 PMID: 1733575
  160. Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms.
    Cancer Res. 1994 Apr 1;54(7 Suppl):1976s-1981s PMID: 8137323
  161. Mitochondrial dysfunction, persistently elevated levels of reactive oxygen species and radiation-induced genomic instability: a review.
    Mutagenesis. 2006 Nov;21(6):361-7 PMID: 17065161
  162. Oxidative stress in the regulation of normal and neoplastic hematopoiesis.
    Antioxid Redox Signal. 2008 Nov;10(11):1923-40 PMID: 18707226
Article Info
Journal
Nature reviews. Drug discovery
Abbr.
Nat Rev Drug Discov
ISSN
1474-1784
DOI
10.1038/nrd2803
Published
2009-07-00
Epub
2009-00-29
Pages
579-91
Language
English
Region
England
NLM ID
101124171
Subset
IM
Grants
NCI NIH HHS · CA085563 · United States
NCI NIH HHS · CA100428 · United States
NCI NIH HHS · CA109041 · United States
External Links
PubMed source DOI: 10.1038/nrd2803 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2