Free radicals: The role of antioxidants and pro-oxidants in cancer development and therapy

Free Radicals: The Role of Antioxidants and Pro-oxidants in Cancer Development

Volumn , Issue , 2014, Pages 1-28

  Cort, Aysegul ^a   Ozben, Tomris ^a  

^a AKDENIZ UNIVERSITY   (Turkey)

Author keywords

Antioxidants; Cancer; Reactive oxygen species

Indexed keywords

EID: 84955352440     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (175)

1. Cadenas E. Biochemistry of oxygen toxicity. Annu. Rev. Biochem., 1989;58:79-110.
2. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol. Interact., 2006 Mar 10;160(1):1-40.
3. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat. Rev Drug. Discov., 2009 Jul;8(7): 579-91.
4. Wang J, Yi J. Cancer cell killing via ROS: to increase or decrease, that is the question. Cancer Biol. Ther., 2008 Dec;7(12):1875-84.
5. Fleury C, Mignotte B, Vayssiere JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie, 2002 Feb-Mar;84(2-3):131-41.
6. Cort A, Timur M, Ozdemir E, Kucuksayan E, Ozben T. Synergistic anticancer activity of curcumin and bleomycin: an in vitro study using human malignant testicular germ cells. Mol. Med. Report., 2012 Jun;5(6):1481-6.
7. Yen CY, Chiu CC, Haung RW, Yeh CC, Huang KJ, Chang KF, et al. Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction. Mutat. Res., 2012 Sep 18;747(2):253-8.
8. Cort A, Ozdemir E, Timur M, Ozben T. Effects of N-acetyl-L-cysteine on bleomycin induced oxidative stress in malignant testicular germ cell tumors. Biochimie, 2012 Dec;94(12):2734-9.
9. Renschler MF. The emerging role of reactive oxygen species in cancer therapy. Eur. J. Cancer, 2004 Sep;40(13):1934-40.
10. Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist. Updat., 2004 Apr;7(2):97-110.
11. Schumacker PT. Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell, 2006 Sep;10(3):175-6.
12. Waris G, Ahsan H. Reactive oxygen species: role in the development of cancer and various chronic conditions. J. Carcinog., 2006;5:14.
13. Trachootham D, Zhou Y, Zhang H, Demizu Y, Chen Z, Pelicano H, et al. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by betaphenylethyl isothiocyanate. Cancer Cell, 2006 Sep;10(3):241-52.
14. Hagen T, D'Amico G, Quintero M, Palacios-Callender M, Hollis V, Lam F, et al. Inhibition of mitochondrial respiration by the anticancer agent 2-methoxyestradiol. Biochem. Biophys. Res, Commun., 2004 Sep 24;322(3):923-9.
15. Chen Y, McMillan-Ward E, Kong J, Israels SJ, Gibson SB. Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells. Cell Death Differ., 2008 Jan;15(1):171-82.
16. Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis, 2000 Nov;5(5):415-8.
17. Reinehr R, Becker S, Eberle A, Grether-Beck S, Haussinger D. Involvement of NADPH oxidase isoforms and Src family kinases in CD95-dependent hepatocyte apoptosis. J. Biol. Chem., 2005 Jul 22;280(29):27179-94.
18. Wang X, Zhang J, Xu T. Cyclophosphamide as a potent inhibitor of tumor thioredoxin reductase in vivo. Toxicol. Appl. Pharmacol., 2007 Jan 1;218(1):88-95.
19. Benhar M, Engelberg D, Levitzki A. ROS, stress-activated kinases and stress signaling in cancer. EMBO Rep., 2002 May;3(5):420-5.
20. Son YO, Hitron JA, Cheng S, Budhraja A, Zhang Z, Lan Guo N, et al. The dual roles of c-Jun NH2-terminal kinase signaling in Cr(VI)-induced apoptosis in JB6 cells. Toxicol. Sci., 2011 Feb;119(2):335-45.
21. Ahn J, Won M, Choi JH, Kim YS, Jung CR, Im DS, et al. Reactive oxygen speciesmediated activation of the Akt/ASK1/p38 signaling cascade and p21(Cip1) downregulation are required for shikonin-induced apoptosis. Apoptosis, 2013 Jul;18(7):870-81.
22. Liu JM, Pan F, Li L, Liu QR, Chen Y, Xiong XX, et al. Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation. Biochem. Biophys. Res. Commun., 2013 Jun 22.
23. Levine B, Yuan J. Autophagy in cell death: an innocent convict? J. Clin. Invest., 2005 Oct;115(10):2679-88.
24. Cuervo AM. Autophagy: in sickness and in health. Trends Cell Biol., 2004 Feb;14 (2):70-7.
25. Shintani T, Klionsky DJ. Autophagy in health and disease: a double-edged sword. Science, 2004 Nov 5;306(5698):990-5.
26. Huang J, Lam GY, Brumell JH. Autophagy signaling through reactive oxygen species. Antioxid. Redox. Signal., 2011 Jun;14(11):2215-31.
27. Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J., 2007 Apr 4;26(7):1749-60.
28. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature, 1999 Dec 9;402(6762):672-6.
29. Qu X, Yu J, Bhagat G, Furuya N, Hibshoosh H, Troxel A, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest., 2003 Dec;112(12):1809-20.
30. Yue Z, Jin S, Yang C, Levine AJ, Heintz N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl. Acad. Sci. USA, 2003 Dec 9;100(25):15077-82.
31. Ling LU, Tan KB, Lin H, Chiu GN. The role of reactive oxygen species and autophagy in safingol-induced cell death. Cell Death Dis., 2011;2:e129.
32. Gibson SB. A matter of balance between life and death: targeting reactive oxygen species (ROS)-induced autophagy for cancer therapy. Autophagy, 2010 Oct;6(7):835-7.
33. Azad MB, Chen Y, Gibson SB. Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment. Antioxid. Redox. Signal, 2009 Apr;11(4):777-90.
34. Liu B, Cheng Y, Zhang B, Bian HJ, Bao JK. Polygonatum cyrtonema lectin induces apoptosis and autophagy in human melanoma A375 cells through a mitochondriamediated ROS-p38-p53 pathway. Cancer Lett., 2009 Mar 8;275(1):54-60.
35. Rigoulet M, Yoboue ED, Devin A. Mitochondrial ROS generation and its regulation: mechanisms involved in H(2)O(2) signaling. Antioxid. Redox. Signal., 2011 Feb 1;14(3):459-68.
36. Dalby KN, Tekedereli I, Lopez-Berestein G, Ozpolat B. Targeting the prodeath and prosurvival functions of autophagy as novel therapeutic strategies in cancer. Autophagy, 2010 Apr;6(3):322-9.
37. Li ZY, Yang Y, Ming M, Liu B. Mitochondrial ROS generation for regulation of autophagic pathways in cancer. Biochem. Biophys. Res. Commun., 2011 Oct 14;414(1): 5-8.
38. Brunk UT, Dalen H, Roberg K, Hellquist HB. Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts. Free Radic. Biol. Med., 1997;23(4):616-26.
39. Thorpe GW, Fong CS, Alic N, Higgins VJ, Dawes IW. Cells have distinct mechanisms to maintain protection against different reactive oxygen species: oxidative-stressresponse genes. Proc. Natl. Acad. Sci. USA, 2004 Apr 27;101(17):6564-9.
40. Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev., 2011 Apr 1;25(7):717-29.
41. Boonstra J, Post JA. Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells. Gene, 2004 Aug 4;337:1-13.
42. Diaz-Moralli S, Tarrado-Castellarnau M, Miranda A, Cascante M. Targeting cell cycle regulation in cancer therapy. Pharmacol. Ther., 2013 May;138(2):255-71.
43. Conklin KA. Cancer chemotherapy and antioxidants. J. Nutr., 2004 Nov;134(11): 3201S-4S.
44. Conklin KA. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr. Cancer Ther., 2004 Dec;3(4):294-300.
45. Ralph SJ, Rodriguez-Enriquez S, Neuzil J, Moreno-Sanchez R. Bioenergetic pathways in tumor mitochondria as targets for cancer therapy and the importance of the ROSinduced apoptotic trigger. Mol. Aspects Med., 2010 Feb;31(1):29-59.
46. Zhang Y, Zhao W, Zhang HJ, Domann FE, Oberley LW. Overexpression of copper zinc superoxide dismutase suppresses human glioma cell growth. Cancer Res., 2002 Feb 15;62(4):1205-12.
47. Deshpande SS, Irani K. Oxidant signalling in carcinogenesis: a commentary. Hum. Exp. Toxicol., 2002 Feb;21(2):63-4.
48. Verbon EH, Post JA, Boonstra J. The influence of reactive oxygen species on cell cycle progression in mammalian cells. Gene, 2012 Dec 10;511(1):1-6.
49. Inoguchi T, Sonta T, Tsubouchi H, Etoh T, Kakimoto M, Sonoda N, et al. Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: role of vascular NAD(P)H oxidase. J. Am. Soc. Nephrol., 2003 Aug;14(8 Suppl 3):S227-32.
50. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol. Cell, 2012 Oct 26;48(2):158-67.
51. Zhang J, Khvorostov I, Hong JS, Oktay Y, Vergnes L, Nuebel E, et al. UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells. EMBO J., 2011 Dec 14;30(24):4860-73.
52. Cho YM, Kwon S, Pak YK, Seol HW, Choi YM, Park do J, et al. Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells. Biochem. Biophys. Res. Commun., 2006 Oct 6;348(4):1472-8.
53. Prigione A, Adjaye J. Modulation of mitochondrial biogenesis and bioenergetic metabolism upon in vitro and in vivo differentiation of human ES and iPS cells. Int. J. Dev. Biol., 2010;54(11-12):1729-41.
54. Tormos KV, Anso E, Hamanaka RB, Eisenbart J, Joseph J, Kalyanaraman B, et al. Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab., 2011 Oct 5;14(4):537-44.
55. Owusu-Ansah E, Banerjee U. Reactive oxygen species prime Drosophila haematopoietic progenitors for differentiation. Nature, 2009 Sep 24;461(7263):537-41.
56. Hofseth LJ, Ying L. Identifying and defusing weapons of mass inflammation in carcinogenesis. Biochim. Biophys. Acta., 2006 Jan;1765(1):74-84.
57. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell, 2010 Mar 19;140(6):883-99.
58. Grivennikov SI, Karin M. Inflammation and oncogenesis: a vicious connection. Curr. Opin. Genet. Dev., 2010 Feb;20(1):65-71.
59. Gonda TA, Tu S, Wang TC. Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle, 2009 Jul 1;8(13):2005-13.
60. Ekbom A, Helmick C, Zack M, Adami HO. Increased risk of large-bowel cancer in Crohn's disease with colonic involvement. Lancet, 1990 Aug 11;336(8711):357-9.
61. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer. A population-based study. N. Engl. J. Med., 1990 Nov 1;323(18):1228-33.
62. Gillen CD, Walmsley RS, Prior P, Andrews HA, Allan RN. Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut, 1994 Nov;35(11):1590-2.
63. Ekbom A, McLaughlin JK, Nyren O. Pancreatitis and the risk of pancreatic cancer. N. Engl. J. Med., 1993 Nov 11;329(20):1502-3.
64. Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology, 2006 Feb;130(2):323-33; quiz 591.
65. Feld JJ, Hoofnagle JH. Mechanism of action of interferon and ribavirin in treatment of hepatitis C. Nature, 2005 Aug 18;436(7053):967-72.
66. Estruch R, Sacanella E, Badia E, Antunez E, Nicolas JM, Fernandez-Sola J, et al. Different effects of red wine and gin consumption on inflammatory biomarkers of atherosclerosis: a prospective randomized crossover trial. Effects of wine on inflammatory markers. Atherosclerosis, 2004 Jul;175(1):117-23.
67. Luceri C, Caderni G, Sanna A, Dolara P. Red wine and black tea polyphenols modulate the expression of cycloxygenase-2, inducible nitric oxide synthase and glutathionerelated enzymes in azoxymethane-induced f344 rat colon tumors. J. Nutr., 2002 Jun;132(6):1376-9.
68. Wannamethee SG, Lowe GD, Rumley A, Bruckdorfer KR, Whincup PH. Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis. Am. J. Clin. Nutr., 2006 Mar;83(3):567-74; quiz 726-7.
69. Sanchez-Moreno C, Cano MP, de Ancos B, Plaza L, Olmedilla B, Granado F, et al. High-pressurized orange juice consumption affects plasma vitamin C, antioxidative status and inflammatory markers in healthy humans. J. Nutr., 2003 Jul;133(7):2204-9.
70. Peng G, Dixon DA, Muga SJ, Smith TJ, Wargovich MJ. Green tea polyphenol (-)- epigallocatechin-3-gallate inhibits cyclooxygenase-2 expression in colon carcinogenesis. Mol. Carcinog., 2006 May;45(5):309-19.
71. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci., 2006 Mar 27;78(18):2081-7.
72. Ide N, Lau BH. Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa b activation. J. Nutr., 2001 Mar;131(3s):1020S-6S.
73. Poljsak B, Suput D, Milisav I. Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants. Oxid. Med. Cell Longev., 2013;2013:956792.
74. Willett WC. The Mediterranean diet: science and practice. Public Health Nutr., 2006 Feb;9(1A):105-10.
75. Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. Vitamin C exhibits pro-oxidant properties. Nature, 1998 Apr 9;392(6676):559.
76. Palozza P. Pro-oxidant actions of carotenoids in biologic systems. Nutr. Rev., 1998 Sep;56(9):257-65.
77. Ju J, Picinich SC, Yang Z, Zhao Y, Suh N, Kong AN, et al. Cancer-preventive activities of tocopherols and tocotrienols. Carcinogenesis, 2010 Apr;31(4):533-42.
78. Yang CS, Suh N. Cancer prevention by different forms of tocopherols. Top Curr. Chem., 2013;329:21-33.
79. Zarogoulidis P, Cheva A, Zarampouka K, Huang H, Li C, Huang Y, et al. Tocopherols and tocotrienols as anticancer treatment for lung cancer: future nutrition. J. Thorac. Dis., 2013 Jun;5(3):349-52.
80. Wang X, Thomas B, Sachdeva R, Arterburn L, Frye L, Hatcher PG, et al. Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress. Proc. Natl. Acad. Sci. USA, 2006 Mar 7;103(10):3604-9.
81. Cornwell DG, Williams MV, Wani AA, Wani G, Shen E, Jones KH. Mutagenicity of tocopheryl quinones: evolutionary advantage of selective accumulation of dietary alpha-tocopherol. Nutr. Cancer, 2002;43(1):111-8.
82. Lotan Y, Goodman PJ, Youssef RF, Svatek RS, Shariat SF, Tangen CM, et al. Evaluation of vitamin E and selenium supplementation for the prevention of bladder cancer in SWOG coordinated SELECT. J. Urol., 2012 Jun;187(6):2005-10.
83. Proteggente AR, Pannala AS, Paganga G, Van Buren L, Wagner E, Wiseman S, et al. The antioxidant activity of regularly consumed fruit and vegetables reflects their phenolic and vitamin C composition. Free Radic. Res., 2002 Feb;36(2):217-33.
84. Weijl NI, Elsendoorn TJ, Lentjes EG, Hopman GD, Wipkink-Bakker A, Zwinderman AH, et al. Supplementation with antioxidant micronutrients and chemotherapy-induced toxicity in cancer patients treated with cisplatin-based chemotherapy: a randomised, double-blind, placebo-controlled study. Eur. J. Cancer, 2004 Jul;40(11):1713-23.
85. Fuchs-Tarlovsky V, Bejarano-Rosales M, Gutierrez-Salmean G, Casillas MA, Lopez- Alvarenga JC, Ceballos-Reyes GM. [Effect of antioxidant supplementation over oxidative stress and quality of life in cervical cancer]. Nutr. Hosp., 2011 Jul- Aug;26(4):819-26.
86. Israel L, Hajji O, Grefft-Alami A, Desmoulins D, Succari M, Cals MJ, et al. [Vitamin A augmentation of the effects of chemotherapy in metastatic breast cancers after menopause. Randomized trial in 100 patients]. Ann. Med. Interne, (Paris). 1985;136(7): 551-4.
87. Abdel-Latif MM, Raouf AA, Sabra K, Kelleher D, Reynolds JV. Vitamin C enhances chemosensitization of esophageal cancer cells in vitro. J. Chemother, 2005 Oct;17(5): 539-49.
88. Gallicchio L, Boyd K, Matanoski G, Tao XG, Chen L, Lam TK, et al. Carotenoids and the risk of developing lung cancer: a systematic review. Am. J. Clin. Nutr., 2008 Aug; 88 (2): 372-83.
89. Tanvetyanon T, Bepler G. Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers: a meta-analysis and evaluation of national brands. Cancer, 2008 Jul 1;113(1):150-7.
90. Jeon YJ, Myung SK, Lee EH, Kim Y, Chang YJ, Ju W, et al. Effects of beta-carotene supplements on cancer prevention: meta-analysis of randomized controlled trials. Nutr. Cancer, 2011 Nov;63(8):1196-207.
91. Yeon JY, Suh YJ, Kim SW, Baik HW, Sung CJ, Kim HS, et al. Evaluation of dietary factors in relation to the biomarkers of oxidative stress and inflammation in breast cancer risk. Nutrition, 2011 Sep;27(9):912-8.
92. Lin PC, Lee MY, Wang WS, Yen CC, Chao TC, Hsiao LT, et al. N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer, 2006 May;14(5):484-7.
93. Cort A, Timur M, Dursun E, Kucuksayan E, Aslan M, Ozben T. Effects of Nacetylcystein on bleomycin-induced apoptosis in malignant testicular germ cell tumors. J. Physiol. Biochem., 2012 Dec;68(4):555-62.
94. Zhang M, Swarts SG, Yin L, Liu C, Tian Y, Cao Y, et al. Antioxidant properties of quercetin. Adv. Exp. Med. Biol., 2011;701:283-9.
95. Samuel T, Fadlalla K, Turner T, Yehualaeshet TE. The flavonoid quercetin transiently inhibits the activity of taxol and nocodazole through interference with the cell cycle. Nutr. Cancer, 2010;62(8):1025-35.
96. Lorusso D, Ferrandina G, Greggi S, Gadducci A, Pignata S, Tateo S, et al. Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients. Ann. Oncol., 2003 Jul;14(7):1086-93.
97. Komaki R, Lee JS, Kaplan B, Allen P, Kelly JF, Liao Z, et al. Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: preliminary results. Semin. Radiat. Oncol., 2002 Jan;12(1 Suppl 1):46-9.
98. Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, et al. Chemopreventive and therapeutic effects of curcumin. Cancer Lett., 2005 Jun 8;223(2):181-90.
99. Hanif R, Qiao L, Shiff SJ, Rigas B. Curcumin, a natural plant phenolic food additive, inhibits cell proliferation and induces cell cycle changes in colon adenocarcinoma cell lines by a prostaglandin-independent pathway. J. Lab. Clin. Med., 1997 Dec;130(6): 576-84.
100. Ramachandran C, You W. Differential sensitivity of human mammary epithelial and breast carcinoma cell lines to curcumin. Breast Cancer Res. Treat., 1999 Apr;54(3): 269-78.
101. Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res., 2003 Jan-Feb;23(1A):363-98.
102. Cort A, Timur M, Ozdemir E, Kucuksayan E, Ozben T. Synergistic anticancer activity of curcumin and bleomycin: an in vitro study using human malignant testicular germ cells. Mol. Med. Rep., 2012 Jun;5(6):1481-6.
103. Cort A, Ozdemir E, Timur M, Ozben T. Effects of curcumin on bleomycininduced oxidative stress in malignant testicular germ cell tumors. Mol. Med. Rep., 2012 Oct;6 (4):860-6.
104. Tikoo K, Sane MS, Gupta C. Tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates its anti-cancer activity: potential role of tannins in cancer chemotherapy. Toxicol. Appl. Pharmacol., 2011 Mar 15;251(3):191-200.
105. Li W, Xu B, Xu J, Wu XL. Procyanidins produce significant attenuation of doxorubicin-induced cardiotoxicity via suppression of oxidative stress. Basic Clin. Pharmacol. Toxicol., 2009 Mar;104(3):192-7.
106. Lambert JD, Elias RJ. The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Arch. Biochem. Biophys., 2010 Sep 1;501(1) :65-72.
107. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 1997 Jan 10;275(5297):218-20.
108. Harikumar KB, Kunnumakkara AB, Sethi G, Diagaradjane P, Anand P, Pandey MK, et al. Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int. J. Cancer, 2010 Jul 15;127(2):257-68.
109. Colin D, Gimazane A, Lizard G, Izard JC, Solary E, Latruffe N, et al. Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluorouracil sensitivity in human derived colon cancer cells. Int. J. Cancer, 2009 Jun 15;124(12):2780-8.
110. Aires V, Limagne E, Cotte AK, Latruffe N, Ghiringhelli F, Delmas D. Resveratrol metabolites inhibit human metastatic colon cancer cells progression and synergize with chemotherapeutic drugs to induce cell death. Mol. Nutr. Food Res., 2013 Jul;57(7): 1170-81.
111. Tabrez S, Priyadarshini M, Urooj M, Shakil S, Ashraf GM, Khan MS, et al. Cancer chemoprevention by polyphenols and their potential application as nanomedicine. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev., 2013;31(1):67-98.
112. Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Anti-tumor effect of ascorbic acid, lysine, proline, arginine, and epigallocatechin gallate on prostate cancer cell lines PC-3, LNCaP, and DU145. Res. Commun. Mol. Pathol. Pharmacol., 2004; 115-116:251-64.
113. Roomi MW, Roomi NW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. Modulation of N-methyl-N-nitrosourea induced mammary tumors in Sprague-Dawley rats by combination of lysine, proline, arginine, ascorbic acid and green tea extract. Breast Cancer Res., 2005;7(3):R291-5.
114. Harakeh S, Diab-Assaf M, Niedzwiecki A, Khalife J, Abu-El-Ardat K, Rath M. Apoptosis induction by Epican Forte in HTLV-1 positive and negative malignant Tcells. Leuk. Res., 2006 Jul;30(7):869-81.
115. Harakeh S, Abdel-Massih RM, Gil PR, Sperling RA, Meinhardt A, Niedwiecki A, et al. The effect of PEG-coated gold nanoparticles on the anti-proliferative potential of Specific Nutrient Synergy. Nanotoxicology, 2010 Jun;4(2):177-85.
116. Roomi MW, Ivanov V, Netke S, Kalinovsky T, Niedzwiecki A, Rath M. In vivo and in vitro antitumor effect of ascorbic acid, lysine, proline and green tea extract on human melanoma cell line A2058. In Vivo. 2006 Jan-Feb;20(1):25-32.
117. Roomi MW, Roomi NW, Kalinovsky T, Niedzwiecki A, Rath M. In vivo and In vitro effect of a nutrient mixture on human hepatocarcinoma cell line SK-HEP-1. Exp. Oncol., 2010 Jul;32(2):84-91.
118. Mukhtar H, Ahmad N. Cancer chemoprevention: future holds in multiple agents. Toxicol. Appl. Pharmacol., 1999 Aug 1;158(3):207-10.
119. Sporn MB, Liby KT. NRF2 and cancer: the good, the bad and the importance of context. Nat. Rev. Cancer, 2012 Aug;12(8):564-71.
120. Perera RM, Bardeesy N. Cancer: when antioxidants are bad. Nature, 2011 Jul 7;475(7354):43-4.
121. Wang XJ, Sun Z, Villeneuve NF, Zhang S, Zhao F, Li Y, et al. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis, 2008 Jun;29(6):1235-43.
122. Shen G, Xu C, Hu R, Jain MR, Nair S, Lin W, et al. Comparison of (-)- epigallocatechin-3-gallate elicited liver and small intestine gene expression profiles between C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice. Pharm. Res., 2005 Nov;22 (11):1805-20.
123. Yuan JH, Li YQ, Yang XY. Inhibition of epigallocatechin gallate on orthotopic colon cancer by upregulating the Nrf2-UGT1A signal pathway in nude mice. Pharmacology, 2007;80(4):269-78.
124. Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro AL, Pronzato MA, et al. Role of glutathione in cancer progression and chemoresistance. Oxid. Med. Cell Longev., 2013;2013:972913.
125. Carretero J, Obrador E, Anasagasti MJ, Martin JJ, Vidal-Vanaclocha F, Estrela JM. Growth-associated changes in glutathione content correlate with liver metastatic activity of B16 melanoma cells. Clin. Exp. Metastasis., 1999;17(7):567-74.
126. Carretero J, Obrador E, Esteve JM, Ortega A, Pellicer JA, Sempere FV, et al. Tumoricidal activity of endothelial cells. Inhibition of endothelial nitric oxide production abrogates tumor cytotoxicity induced by hepatic sinusoidal endothelium in response to B16 melanoma adhesion in vitro. J. Biol. Chem., 2001 Jul 13;276 (28):25775-82.
127. D'Souza RJ, Phillips HM, Jones PW, Strange RC, Aber GM. Interactions of hydrogen peroxide with interleukin-6 and platelet-derived growth factor in determining mesangial cell growth: effect of repeated oxidant stress. Clin. Sci., (Lond). 1993 Dec;85(6):747- 51.
128. Alliangana DM. Effects of beta-carotene, flavonoid quercitin and quinacrine on cell proliferation and lipid peroxidation breakdown products in BHK-21 cells. East Afr. Med. J., 1996 Nov;73(11):752-7.
129. Chang MC, Chan CP, Wang YJ, Lee PH, Chen LI, Tsai YL, et al. Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization. Toxicol. Appl. Pharmacol., 2007 Jan 15;218(2):143-51.
130. Dypbukt JM, Ankarcrona M, Burkitt M, Sjoholm A, Strom K, Orrenius S, et al. Different pro-oxidant levels stimulate growth, trigger apoptosis, or produce necrosis of insulin-secreting RINm5F cells. The role of intracellular polyamines. J. Biol. Chem., 1994 Dec 2;269(48):30553-60.
131. Halliwell B. Oxidative stress and cancer: have we moved forward? Biochem. J., 2007 Jan 1;401(1):1-11.
132. Kong Q, Lillehei KO. Antioxidant inhibitors for cancer therapy. Med. Hypotheses, 1998 Nov;51(5):405-9.
133. Siddiqui IA, Adhami VM, Saleem M, Mukhtar H. Beneficial effects of tea and its polyphenols against prostate cancer. Mol. Nutr. Food Res., 2006 Feb;50(2):130-43.
134. Seifried HE, Anderson DE, Fisher EI, Milner JA. A review of the interaction among dietary antioxidants and reactive oxygen species. J. Nutr. Biochem., 2007 Sep;18(9): 567-79.
135. Schloss JM, Colosimo M, Airey C, Masci PP, Linnane AW, Vitetta L. Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): A systematic review. Clin. Nutr., 2013 Apr 13.
136. Hochster HS, Grothey A, Childs BH. Use of calcium and magnesium salts to reduce oxaliplatin-related neurotoxicity. J. Clin. Oncol., 2007 Sep 1;25(25):4028-9.
137. Smyth JF, Bowman A, Perren T, Wilkinson P, Prescott RJ, Quinn KJ, et al. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Ann. Oncol., 1997 Jun;8(6):569-73.
138. Maestri A, De Pasquale Ceratti A, Cundari S, Zanna C, Cortesi E, Crino L. A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy. Tumori, 2005 Mar-Apr;91(2):135-8.
139. Puglia CD, Powell SR. Inhibition of cellular antioxidants: a possible mechanism of toxic cell injury. Environ. Health Perspect., 1984 Aug;57:307-11.
140. Palozza P, Serini S, Di Nicuolo F, Piccioni E, Calviello G. Pro-oxidant effects of betacarotene in cultured cells. Mol. Aspects Med., 2003 Dec;24(6):353-62.
141. Pathi SS, Lei P, Sreevalsan S, Chadalapaka G, Jutooru I, Safe S. Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutr. Cancer, 2011;63(7):1133-42.
142. Carocho M, Ferreira IC. A review on antioxidants, pro-oxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food Chem. Toxicol., 2013 Jan;51:15-25.
143. Rajendran P, Li F, Manu KA, Shanmugam MK, Loo SY, Kumar AP, et al. gamma- Tocotrienol is a novel inhibitor of constitutive and inducible STAT3 signalling pathway in human hepatocellular carcinoma: potential role as an antiproliferative, pro-apoptotic and chemosensitizing agent. Br. J. Pharmacol., 2011 May;163(2):283-98.
144. Kanai K, Kikuchi E, Mikami S, Suzuki E, Uchida Y, Kodaira K, et al. Vitamin E succinate induced apoptosis and enhanced chemosensitivity to paclitaxel in human bladder cancer cells in vitro and in vivo. Cancer Sci., 2010 Jan;101(1):216-23.
145. Lim SJ, Choi MK, Kim MJ, Kim JK. Alpha-tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells. Exp. Mol. Med., 2009 Oct 31;41(10):737-45.
146. Tang J, Fu Q, Wang Y, Racette K, Wang D, Liu F. Vitamin E reverses multidrug resistance in vitro and in vivo. Cancer Lett., 2013 Aug 9;336(1):149-57.
147. Sylvester PW, Ayoub NM. Tocotrienols Target PI3K/Akt Signaling in Anti-Breast Cancer Therapy. Anticancer. Agents Med. Chem., 2013 Sep;13(7):1039-47.
148. Felipe KB, Benites J, Glorieux C, Sid B, Valenzuela M, Kviecinski MR, et al. Antiproliferative effects of phenylaminonaphthoquinones are increased by ascorbate and associated with the appearance of a senescent phenotype in human bladder cancer cells. Biochem. Biophys. Res. Commun., 2013 Apr 19;433(4):573-8.
149. Park JH, Davis KR, Lee G, Jung M, Jung Y, Park J, et al. Ascorbic acid alleviates toxicity of paclitaxel without interfering with the anticancer efficacy in mice. Nutr. Res., 2012 Nov;32(11):873-83.
150. Frank J, Flaccus A, Schwarz C, Lambert C, Biesalski HK. Ascorbic acid suppresses cell death in rat DS-sarcoma cancer cells induced by 5-aminolevulinic acid-based photodynamic therapy. Free Radic. Biol. Med., 2006 Mar 1;40(5):827-36.
151. Kontek R, Drozda R, Sliwinski M, Grzegorczyk K. Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human lymphocytes from healthy individuals and cancer patients. Toxicol. In Vitro, 2010 Mar;24(2):417-24.
152. Croker AK, Allan AL. Inhibition of aldehyde dehydrogenase (ALDH) activity reduces chemotherapy and radiation resistance of stem-like ALDHhiCD44(+) human breast cancer cells. Breast Cancer Res. Treat, 2012 May;133(1):75-87.
153. Arrieta O, Gonzalez-De la Rosa CH, Arechaga-Ocampo E, Villanueva-Rodriguez G, Ceron-Lizarraga TL, Martinez-Barrera L, et al. Randomized phase II trial of All-transretinoic acid with chemotherapy based on paclitaxel and cisplatin as first-line treatment in patients with advanced non-small-cell lung cancer. J. Clin. Oncol., 2010 Jul 20;28 (21):3463-71.
154. Karmakar S, Banik NL, Ray SK. Combination of all-trans retinoic acid and paclitaxelinduced differentiation and apoptosis in human glioblastoma U87MG xenografts in nude mice. Cancer, 2008 Feb 1;112(3):596-607.
155. Hung SH, Lee FP, Su CH, Tseng H. Effect of all-trans retinoic acid on the growth of two nasopharyngeal cancer cell lines and its treatment potential in combination with cisplatin. Eur. Arch. Otorhinolaryngol., 2013 Feb;270(2):695-704.
156. Ping SY, Hour TC, Lin SR, Yu DS. Taxol synergizes with antioxidants in inhibiting hormal refractory prostate cancer cell growth. Urol. Oncol., 2010 Mar-Apr;28(2):170-9.
157. Johnson JL, Gonzalez de Mejia E. Interactions between dietary flavonoids apigenin or luteolin and chemotherapeutic drugs to potentiate anti-proliferative effect on human pancreatic cancer cells, in vitro. Food Chem. Toxicol., 2013 Jul 18.
158. Kang Y, Park MA, Heo SW, Park SY, Kang KW, Park PH, et al. The radio-sensitizing effect of xanthohumol is mediated by STAT3 and EGFR suppression in doxorubicinresistant MCF-7 human breast cancer cells. Biochim. Biophys. Acta., 2013 Mar;1830(3) :2638-48.
159. Qin J, Wang Y, Bai Y, Yang K, Mao Q, Lin Y, et al. Epigallocatechin-3-gallate inhibits bladder cancer cell invasion via suppression of NF-kappaBmediated matrix metalloproteinase-9 expression. Mol. Med. Rep., 2012 Nov;6(5):1040-4.
160. Yang YI, Lee KT, Park HJ, Kim TJ, Choi YS, Shih Ie M, et al. Tectorigenin sensitizes paclitaxel-resistant human ovarian cancer cells through downregulation of the Akt and NFkappaB pathway. Carcinogenesis, 2012 Dec;33(12):2488-98.
161. Lin X, Wu G, Huo WQ, Zhang Y, Jin FS. Resveratrol induces apoptosis associated with mitochondrial dysfunction in bladder carcinoma cells. Int. J. Urol., 2012 Aug;19(8): 757-64.
162. Periasamy VS, Alshatwi AA. Tea polyphenols modulate antioxidant redox system on cisplatin-induced reactive oxygen species generation in a human breast cancer cell. Basic Clin. Pharmacol. Toxicol., 2013 Jun;112(6):374-84.
163. Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol. Cell Biochem., 2004 Nov;266(1-2):37-56.
164. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007;39(1):44-84.
165. Valdez BC, Murray D, Nieto Y, Li Y, Wang G, Champlin RE, et al. Synergistic cytotoxicity of the DNA alkylating agent busulfan, nucleoside analogs and suberoylanilide hydroxamic acid in lymphoma cell lines. Leuk Lymphoma, 2012 May;53(5):973-81.
166. Ledermann JA, Gabra H, Jayson GC, Spanswick VJ, Rustin GJ, Jitlal M, et al. Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer. Clin. Cancer Res., 2010 Oct 1;16(19):4899-905.
167. LaPointe NE, Morfini G, Brady ST, Feinstein SC, Wilson L, Jordan MA. Effects of eribulin, vincristine, paclitaxel and ixabepilone on fast axonal transport and kinesin-1 driven microtubule gliding: implications for chemotherapy-induced peripheral neuropathy. Neurotoxicology, 2013 Jul;37:231-9.
168. Ozben T. Oxidative stress and apoptosis: impact on cancer therapy. J. Pharm. Sci., 2007 Sep;96(9):2181-96.
169. Bishayee A. Cancer prevention and treatment with resveratrol: from rodent studies to clinical trials. Cancer Prev. Res., (Phila). 2009 May;2(5):409-18.
170. Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat. Rev. Cancer, 2009 Jun;9(6):429-39.
171. Conklin KA. Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr. Cancer, 2000;37(1):1-18.
172. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat Rev., 2007 Aug;33(5):407- 18.
173. Lissoni P, Chilelli M, Villa S, Cerizza L, Tancini G. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J. Pineal. Res., 2003 Aug;35(1):12-5.
174. Cerea G, Vaghi M, Ardizzoia A, Villa S, Bucovec R, Mengo S, et al. Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracilcontaining combinations. Anticancer Res., 2003 Mar-Apr;23(2C):1951-4.
175. Fuchs-Tarlovsky V. Role of antioxidants in cancer therapy. Nutrition, 2013 Jan;29(1):15-21.