Antioxidant supplementation on cancer risk and during cancer therapy: An update

Current Topics in Medicinal Chemistry

Volumn 15, Issue 2, 2015, Pages 170-178

  Ozben, Tomris ^a  

^a AKDENIZ UNIVERSITY   (Turkey)

Author keywords

Antioxidants; Cancer; Chemotherapeutic agents; Oxidative stress; Radiation; Reactive oxygen species; Supplements

Indexed keywords

ACETYLCYSTEINE; ALPHA CAROTENE; ALPHA TOCOPHEROL; AMIFOSTINE; ANTIOXIDANT; ASCORBIC ACID; BETA CAROTENE; CARBOPLATIN; CAROTENOID; CISPLATIN; CURCUMIN; DOXORUBICIN; EPIGALLOCATECHIN GALLATE; FLAVONOID; GLUTATHIONE; NICOTINIC ACID; PACLITAXEL; PENTOXIFYLLINE; QUERCETIN; REACTIVE OXYGEN METABOLITE; RESVERATROL; RETINOL; RETINOL PALMITATE; SELENIUM; UBIDECARENONE; ANTINEOPLASTIC AGENT;

ANTIOXIDANT ACTIVITY; APOPTOSIS; ARTICLE; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RISK; CANCER THERAPY; CELL DEATH; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG SAFETY; HUMAN; META ANALYSIS (TOPIC); NONHUMAN; OVERALL SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIDE EFFECT; SYSTEMATIC REVIEW (TOPIC); TUMOR GROWTH; DRUG EFFECTS; METABOLISM; NEOPLASMS; PATHOLOGY; RISK FACTOR;

ANTINEOPLASTIC AGENTS; ANTIOXIDANTS; APOPTOSIS; HUMANS; NEOPLASMS; REACTIVE OXYGEN SPECIES; RISK FACTORS;

EID: 84926293588     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026615666141209160918     Document Type: Article

References (108)

1. Velicer, C.M.; Ulrich, C.M.Vitamin and mineral supplement use among US adults after cancer diagnosis: a systematic review. J. Clin. Oncol., 2008, 26(4), 665-673.
2. Palmer, S.Therapeutic Controversy — Is Supplementing Cancer Treatment With Antioxidants Helpful or Harmful? Today’s Dietitian., 2010, 12(4), 26.
3. Seely, D.M.; Weeks, L.C.; Young, S.A. Systematic review of integrative oncology programs. Curr. Oncol., 2012, 19(6), e436-461.
4. Nakayama, A.; Alladin, K.P.; Igbokwe, O.; White, J.D. Systematic review: generating evidence-based guidelines on the concurrent use of dietary antioxidants and chemotherapy or radiotherapy. Cancer Invest., 2011, 29(10), 655-667.
5. Ozben, T. Oxidative stress and apoptosis: impact on cancer therapy. J. Pharm. Sci., 2007, 96(9), 2181-2196.
6. Trachootham, D.; Alexandre, J.; Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat. Rev. Drug, Discov., 2009, 8(7), 579-591.
7. Conklin, K.A. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr. Cancer Ther., 2004, 3(4), 294-300.
8. Lawenda, B.D.; Kelly, K.M.; Ladas, E.J.; Sagar, S.M.; Vickers, A.; Blumberg, J.B.Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst., 2008, 100(11), 773-783.
9. Seifried, H.E.; McDonald, S.S.; Anderson, D.E.; Greenwald, P.; Milner, J.A. The antioxidant conundrum in cancer. Cancer Res. 2003, 63(15), 4295-4298.
10. Moss, R.W.Should patients undergoing chemotherapy and radiotherapy be prescribed antioxidants? Integr Cancer Ther., 2006, 5(1), 63-82.
11. Salganik, R.I. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr., 2001, 20(5 Suppl), 464S-472S; discussion 473S-475S.
12. Akbas, H.S.; Timur, M.; Ozben, T. Concurrent Use of Antioxidants in Cancer Therapy: An Update Exp.Rev. Clin. Immunol., 2006; 2(6), 931-939.
13. Cort, A., Ozben, T. In: Free Radicals The role of antioxidants and pro-oxidants in cancer development; B. Stone Ed.; Nova Science Publishers, Inc. : New York, 2014, pp. 1-29.
14. Drisko, J.A.; Chapman, J.; Hunter, V.J.The use of antioxidant therapies during chemotherapy. Gynecol. Oncol., 2003, 88(3), 434-439.
15. Prasad, K.N.; Kumar, A.; Kochupillai, V.; Cole, W.C. High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy. J. Am. Coll. Nutr., 1999, 18(1), 13-25.
16. Simone, C.B., 2nd; Simone, N.L.; Simone, V.; Simone, C.B. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, Part 2. Altern. Ther. Health Med., 2007, 13(2), 40-47.
17. Simone, C.B., 2nd; Simone, N.L.; Simone, V.; Simone, C.B. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1. Altern. Ther. Health Med., 2007, 13(1), 22-28.
18. Bjelakovic, G.; Nikolova, D.; Simonetti, R.G.; Gluud, C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet, 2004, 364(9441), 1219-1228.
19. Lippman, S.M.; Klein, E.A.; Goodman, P.J.; Lucia, M.S.; Thompson, I.M.; Ford, L.G.; Parnes, H.L.; Minasian, L.M.; Gaziano, J.M.; Hartline, J.A.; Parsons, J.K.; Bearden, J.D., 3rd; Crawford, E.D.; Goodman, G.E.; Claudio, J.; Winquist, E.; Cook, E.D.; Karp, D.D.; Walther, P.; Lieber, M.M.; Kristal, A.R.; Darke, A.K.; Arnold, K.B.; Ganz, P.A.; Santella, R.M.; Albanes, D.; Taylor, P.R.; Probstfield, J.L.; Jagpal, T.J.; Crowley, J.J.; Meyskens, F.L., Jr.; Baker, L.H.; Coltman, C.A. Jr. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA, 2009, 301(1), 39-51.
20. Klein, E.A.; Thompson, I.M., Jr.; Tangen, C.M.; Crowley, J.J.; Lucia, M.S.; Goodman, P.J.; Minasian, L.M.; Ford, L.G.; Parnes, H.L.; Gaziano, J.M.; Karp, D.D.; Lieber, M.M.; Walther, P.J.; Klotz, L.; Parsons, J.K.; Chin, J.L.; Darke, A.K.; Lippman, S.M.; Goodman, G.E.; Meyskens, F.L., Jr.; Baker, L.H. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA, 2011, 306(14), 1549-1556.
21. Blot, W.J.; Li, J.Y.; Taylor, P.R.; Guo, W.; Dawsey, S.; Wang, G.Q.; Yang, C.S.; Zheng, S.F.; Gail, M.; Li, G.Y., et al.Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and diseasespecific mortality in the general population. J. Natl. Cancer Inst., 1993, 85(18), 1483-1492.
22. Qiao, Y.L.; Dawsey, S.M.; Kamangar, F.; Fan, J.H.; Abnet, C.C.; Sun, X.D.; Johnson, L.L.; Gail, M.H.; Dong, Z.W.; Yu, B.; Mark, S.D.; Taylor, P.R. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. J. Natl. Cancer Inst., 2009, 101(7), 507-518.
23. Rautalahti, M.T.; Virtamo, J.R.; Taylor, P.R.; Heinonen, O.P.; Albanes, D.; Haukka, J.K.; Edwards, B.K.; Karkkainen, P.A.; Stolzenberg-Solomon, R.Z.; Huttunen, J.The effects of supplementation with alpha-tocopherol and beta-carotene on the incidence and mortality of carcinoma of the pancreas in a randomized, controlled trial. Cancer, 1999, 86(1), 37-42.
24. Virtamo, J.; Edwards, B.K.; Virtanen, M.; Taylor, P.R.; Malila, N.; Albanes, D.; Huttunen, J.K.; Hartman, A.M.; Hietanen, P.; Maenpaa, H.; Koss, L.; Nordling, S.; Heinonen, O.P.Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland). Cancer Causes Control, 2000, 11(10), 933-939.
25. Albanes, D.; Malila, N.; Taylor, P.R.; Huttunen, J.K.; Virtamo, J.; Edwards, B.K.; Rautalahti, M.; Hartman, A.M.; Barrett, M.J.; Pietinen, P.; Hartman, T.J.; Sipponen, P.; Lewin, K.; Teerenhovi, L.; Hietanen, P.; Tangrea, J.A.; Virtanen, M.; Heinonen, O.P.Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland). Cancer Causes Control., 2000, 11(3), 197-205.
26. Wright, M.E.; Virtamo, J.; Hartman, A.M.; Pietinen, P.; Edwards, B.K.; Taylor, P.R.; Huttunen, J.K.; Albanes, D. Effects of alphatocopherol and beta-carotene supplementation on upper aerodigestive tract cancers in a large, randomized controlled trial. Cancer, 2007, 109(5), 891-898.
27. Wright, M.E.; Weinstein, S.J.; Lawson, K.A.; Albanes, D.; Subar, A.F.; Dixon, L.B.; Mouw, T.; Schatzkin, A.; Leitzmann, M.F. Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study. Cancer Epidemiol.Biomark.Prev., 2007, 16(6), 1128-1135.
28. Omenn, G.S.; Goodman, G.E.; Thornquist, M.D.; Balmes, J.; Cullen, M.R.; Glass, A.; Keogh, J.P.; Meyskens, F.L.; Valanis, B.; Williams, J.H.; Barnhart, S.; Hammar, S.Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med., 1996, 334(18), 1150-1155.
29. Goodman, G.E.; Thornquist, M.D.; Balmes, J.; Cullen, M.R.; Meyskens, F.L., Jr.; Omenn, G.S.; Valanis, B.; Williams, J.H., Jr. The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year followup after stopping beta-carotene and retinol supplements. J. Natl. Cancer Inst., 2004, 96(23), 1743-1750.
30. Neuhouser, M.L.; Barnett, M.J.; Kristal, A.R.; Ambrosone, C.B.; King, I.B.; Thornquist, M.; Goodman, G.G. Dietary supplement use and prostate cancer risk in the Carotene and Retinol Efficacy Trial. Cancer Epidemiol. Biomark.Prev., 2009; 18(8), 2202-2206.
31. Neuhouser, M.L.; Wassertheil-Smoller, S.; Thomson, C.; Aragaki, A.; Anderson, G.L.; Manson, J.E.; Patterson, R.E.; Rohan, T.E.; van Horn, L.; Shikany, J.M.; Thomas, A.; LaCroix, A.; Prentice, R.L. Multivitamin use and risk of cancer and cardiovascular disease in the Women’s Health Initiative cohorts. Arch. Intern. Med., 2009, 169(3), 294-304.
32. Hennekens, C.H.; Buring, J.E.; Manson, J.E.; Stampfer, M.; Rosner, B.; Cook, N.R.; Belanger, C.; LaMotte, F.; Gaziano, J.M.; Ridker, P.M.; Willett, W.; Peto, R. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N. Engl. J. Med., 1996, 334(18), 1145-1149.
33. Lee, I.M.; Cook, N.R.; Manson, J.E.; Buring, J.E.; Hennekens, C.H. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women’s Health Study. J. Natl. Cancer Inst., 1999, 91(24), 2102-2106.
34. Lee, I.M.; Cook, N.R.; Gaziano, J.M.; Gordon, D.; Ridker, P.M.; Manson, J.E.; Hennekens, C.H.; Buring, J.E. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA, 2005, 294(1), 56-65.
35. Hercberg, S.; Galan, P.; Preziosi, P.; Bertrais, S.; Mennen, L.; Malvy, D.; Roussel, A.M.; Favier, A.; Briancon, S. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med., 2004; 164(21), 2335-2342.
36. Hercberg, S.; Ezzedine, K.; Guinot, C.; Preziosi, P.; Galan, P.; Bertrais, S.; Estaquio, C.; Briancon, S.; Favier, A.; Latreille, J.; Malvy, D. Antioxidant supplementation increases the risk of skin cancers in women but not in men. J. Nutr., 2007, 137(9), 2098-2105.
37. Hercberg, S.; Kesse-Guyot, E.; Druesne-Pecollo, N.; Touvier, M.; Favier, A.; Latino-Martel, P.; Briancon, S.; Galan, P. Incidence of cancers, ischemic cardiovascular diseases and mortality during 5-year follow-up after stopping antioxidant vitamins and minerals supplements: a postintervention follow-up in the SU.VI.MAX Study. Int. J. Cancer, 2010, 127(8), 1875-1881.
38. Ezzedine, K.; Latreille, J.; Kesse-Guyot, E.; Galan, P.; Hercberg, S.; Guinot, C.; Malvy, D.Incidence of skin cancers during 5-year follow-up after stopping antioxidant vitamins and mineral supplementation. Eur. J. Cancer, 2010, 46(18), 3316-3322.
39. Lonn, E.; Bosch, J.; Yusuf, S.; Sheridan, P.; Pogue, J.; Arnold, J.M.; Ross, C.; Arnold, A.; Sleight, P.; Probstfield, J.; Dagenais, G.R. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA, 2005, 293(11), 1338-1347.
40. Gaziano, J.M.; Glynn, R.J.; Christen, W.G.; Kurth, T.; Belanger, C.; MacFadyen, J.; Bubes, V.; Manson, J.E.; Sesso, H.D.; Buring, J.E. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA, 2009; 301(1), 52-62.
41. Fortmann, S.P.; Burda, B.U.; Senger, C.A.; Lin, J.S.; Whitlock, E.P.Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force. Ann. Intern. Med., 2013, 159(12), 824-834.
42. Lee, I.M. Antioxidant vitamins in the prevention of cancer. Proc. Assoc. Am. Physicians, 1999, 111(1), 10-15.
43. Bairati, I.; Meyer, F.; Jobin, E.; Gelinas, M.; Fortin, A.; Nabid, A.; Brochet, F.; Tetu, B. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int. J. Cancer, 2006, 119(9), 2221-2224.
44. Ferreira, P.R.; Fleck, J.F.; Diehl, A.; Barletta, D.; Braga-Filho, A.; Barletta, A.; Ilha, L.Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial. Head Neck, 2004; 26(4), 313-321.
45. Lesperance, M.L.; Olivotto, I.A.; Forde, N.; Zhao, Y.; Speers, C.; Foster, H.; Tsao, M.; MacPherson, N.; Hoffer, A. Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study. Breast Cancer Res. Treat., 2002, 76(2), 137-143.
46. Misirlioglu, C.H.; Erkal, H.; Elgin, Y.; Ugur, I.; Altundag, K. Effect of concomitant use of pentoxifylline and alpha-tocopherol with radiotherapy on the clinical outcome of patients with stage IIIB non-small cell lung cancer: a randomized prospective clinical trial. Med. Oncol., 2006, 23(2), 185-189.
47. Lissoni, P.; Meregalli, S.; Nosetto, L.; Barni, S.; Tancini, G.; Fossati, V.; Maestroni, G.Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology., 1996; 53(1), 43-46.
48. Leong, S.S.; Tan, E.H.; Fong, K.W.; Wilder-Smith, E.; Ong, Y.K.; Tai, B.C.; Chew, L.; Lim, S.H.; Wee, J.; Lee, K.M.; Foo, K.F.; Ang, P.; Ang, P.T.Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small-cell lung cancer. J. Clin .Oncol., 2003, 21(9), 1767-1774.
49. Movsas, B.; Scott, C.; Langer, C.; Werner-Wasik, M.; Nicolaou, N.; Komaki, R.; Machtay, M.; Smith, C.; Axelrod, R.; Sarna, L.; Wasserman, T.; Byhardt, R.Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01. J. Clin. Oncol., 2005, 23(10), 2145-2154.
50. Wasserman, T.H.; Brizel, D.M.; Henke, M.; Monnier, A.; Eschwege, F.; Sauer, R.; Strnad, V.Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and-neck cancer: 2-year follow-up of a prospective, randomized, phase III trial. Int. J. Radiat. Oncol. Biol. Phys., 2005, 63(4), 985-990.
51. Wang, J.; Yi, J.Cancer cell killing via ROS: to increase or decrease, that is the question. Cancer Biol. Ther., 2008; 7(12), 1875-1884.
52. Seifried, H.E.; Anderson, D.E.; Fisher, E.I.; Milner, J.A.A review of the interaction among dietary antioxidants and reactive oxygen species. J. Nutr. Biochem., 2007, 18(9), 567-579.
53. Gallicchio, L.; Boyd, K.; Matanoski, G.; Tao, X.G.; Chen, L.; Lam, T.K.; Shiels, M.; Hammond, E.; Robinson, K.A.; Caulfield, L.E.; Herman, J.G.; Guallar, E.; Alberg, A.J.Carotenoids and the risk of developing lung cancer: a systematic review. Am. J. Clin. Nutr., 2008; 88(2), 372-383.
54. 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, 113(1), 150-157.
55. Jeon, Y.J.; Myung, S.K.; Lee, E.H.; Kim, Y.; Chang, Y.J.; Ju, W.; Cho, H.J.; Seo, H.G.; Huh, B.Y.Effects of beta-carotene supplements on cancer prevention: meta-analysis of randomized controlled trials. Nutr. Cancer, 2011, 63(8), 1196-1207.
56. Forman, D.; Altman, D.Vitamins to prevent cancer: supplementary problems. Lancet, 2004, 364(9441), 1193-1194.
57. Sayin, V.I.; Ibrahim, M.X.; Larsson, E.; Nilsson, J.A.; Lindahl, P.; Bergo, M.O.Antioxidants accelerate lung cancer progression in mice. Sci. Transl. Med, 2014, 6(221), 221-215.
58. Ju, J.; Picinich, S.C.; Yang, Z.; Zhao, Y.; Suh, N.; Kong, A.N.; Yang, C.S.Cancer-preventive activities of tocopherols and tocotrienols. Carcinogenesis, 2010, 31(4), 533-542.
59. Yang, C.S.; Suh, N.Cancer prevention by different forms of tocopherols. Top. Curr. Chem., 2013, 329(21-33).
60. Zarogoulidis, P.; Cheva, A.; Zarampouka, K.; Huang, H.; Li, C.; Huang, Y.; Katsikogiannis, N.; Zarogoulidis, K.Tocopherols and tocotrienols as anticancer treatment for lung cancer: future nutrition. J. Thorac. Dis., 2013, 5(3), 349-352.
61. Kristal, A.R.; Darke, A.K.; Morris, J.S.; Tangen, C.M.; Goodman, P.J.; Thompson, I.M.; Meyskens, F.L., Jr.; Goodman, G.E.; Minasian, L.M.; Parnes, H.L.; Lippman, S.M.; Klein, E.A.Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk. J. Natl. Cancer Inst., 2014, 106(3), djt456.
62. Lotan, Y.; Goodman, P.J.; Youssef, R.F.; Svatek, R.S.; Shariat, S.F.; Tangen, C.M.; Thompson, I.M., Jr.; Klein, E.A.Evaluation of vitamin E and selenium supplementation for the prevention of bladder cancer in SWOG coordinated SELECT. J. Urol., 2012, 187(6), 2005-2010.
63. Zetterstrom, R.Nobel Prize 1937 to Albert von Szent-Gyorgyi: identification of vitamin C as the anti-scorbutic factor. Acta. Paediatr., 2009, 98(5), 915-919.
64. Wilson, M.K.; Baguley, B.C.; Wall, C.; Jameson, M.B.; Findlay, M.P.Review of high-dose intravenous vitamin C as an anticancer agent. Asia Pac J. Clin. Oncol., 2014, 10(1), 22-37.
65. Pathi, S.S.; 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), 1133-1142.
66. Weijl, N.I.; Elsendoorn, T.J.; Lentjes, E.G.; Hopman, G.D.; Wipkink-Bakker, A.; Zwinderman, A.H.; Cleton, F.J.; Osanto, S.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, 40(11), 1713-1723.
67. Fuchs-Tarlovsky, V.; Bejarano-Rosales, M.; Gutierrez-Salmean, G.; Casillas, M.A.; Lopez-Alvarenga, J.C.; Ceballos-Reyes, G.M.[Effect of antioxidant supplementation over oxidative stress and quality of life in cervical cancer]. Nutr. Hosp., 2011, 26(4), 819-826.
68. Ma, Y.; Chapman, J.; Levine, M.; Polireddy, K.; Drisko, J.; Chen, Q.High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci. Transl. Med., 2014, 6(222), 222-218.
69. Moertel, C.G.; Fleming, T.R.; Creagan, E.T.; Rubin, J.; O’Connell, M.J.; Ames, M.M.High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N. Engl. J. Med., 1985, 312(3), 137-141.
70. Carocho, M.; Ferreira, I.C.A review on antioxidants, prooxidants and related controversy: natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food Chem. Toxicol., 2013, 51(15-25).
71. Lambert, J.D.; Elias, R.J.The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Arch. Biochem. Biophys., 2010, 501(1), 65-72.
72. Tabrez, S.; Priyadarshini, M.; Urooj, M.; Shakil, S.; Ashraf, G.M.; Khan, M.S.; Kamal, M.A.; Alam, Q.; Jabir, N.R.; Abuzenadah, A.M.; Chaudhary, A.G.; Damanhouri, G.A.Cancer chemoprevention by polyphenols and their potential application as nanomedicine. J. Environ. Sci. Health C. Environ. Carcinog. Ecotoxicol. Rev., 2013, 31(1), 67-98.
73. Harikumar, K.B.; Kunnumakkara, A.B.; Sethi, G.; Diagaradjane, P.; Anand, P.; Pandey, M.K.; Gelovani, J.; Krishnan, S.; Guha, S.; Aggarwal, B.B.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, 127(2), 257-268.
74. Aires, V.; Limagne, E.; Cotte, A.K.; 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, 57(7), 1170-1181.
75. Zhang, M.; Swarts, S.G.; Yin, L.; Liu, C.; Tian, Y.; Cao, Y.; Swarts, M.; Yang, S.; Zhang, S.B.; Zhang, K.; Ju, S.; Olek, D.J., Jr.; Schwartz, L.; Keng, P.C.; Howell, R.; Zhang, L.; Okunieff, P.Antioxidant properties of quercetin. Adv. Exp. Med. Biol., 2011, 701(283-289).
76. Samuel, T.; Fadlalla, K.; Turner, T.; Yehualaeshet, T.E.The flavonoid quercetin transiently inhibits the activity of taxol and nocodazole through interference with the cell cycle. Nutr. Cancer, 2010, 62(8), 1025-1035.
77. Akbas, S.H.; Timur, M.; Ozben, T.The effect of quercetin on topotecan cytotoxicity in MCF-7 and MDA-MB 231 human breast cancer cells. J. Surg. Res., 2005, 125(1), 49-55.
78. Duvoix, A.; Blasius, R.; Delhalle, S.; Schnekenburger, M.; Morceau, F.; Henry, E.; Dicato, M.; Diederich, M.Chemopreventive and therapeutic effects of curcumin. Cancer Lett., 2005, 223(2), 181-190.
79. Aggarwal, B.B.; Kumar, A.; Bharti, A.C.Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res., 2003, 23(1A), 363-398.
80. Cort, A.; Timur, M.; Ozdemir, E.; Ozben, T.Effects of curcumin on bleomycin-induced apoptosis in human malignant testicular germ cells. J. Physiol. Biochem., 2013, 69 (2), 289-96
81. 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, 6(4), 860-866.
82. 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, 5(6), 1481-1486.
83. Conklin, K.A.Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr. Cancer, 2000, 37(1), 1-18.
84. Roller, A.; Weller, M.Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells. Anticancer Res., 1998, 18(6A), 4493-4497.
85. Myers, C.; Bonow, R.; Palmeri, S.; Jenkins, J.; Corden, B.; Locker, G.; Doroshow, J.; Epstein, S.A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by Nacetylcysteine. Semin. Oncol., 1983, 10(1 Suppl 1), 53-55.
86. Unverferth, D.V.; Jagadeesh, J.M.; Unverferth, B.J.; Magorien, R.D.; Leier, C.V.; Balcerzak, S.P.Attempt to prevent doxorubicininduced acute human myocardial morphologic damage with acetylcysteine. J. Natl. Cancer Inst., 1983, 71(5), 917-920.
87. Lin, P.C.; Lee, M.Y.; Wang, W.S.; Yen, C.C.; Chao, T.C.; Hsiao, L.T.; Yang, M.H.; Chen, P.M.; Lin, K.P.; Chiou, T.J.Nacetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer, 2006, 14(5), 484-487.
88. Nisar, S.; Feinfeld, D.A.N-acetylcysteine as salvage therapy in cisplatin nephrotoxicity. Ren. Fail., 2002; 24(4), 529-533.
89. Feghali, J.G.; Liu, W.; Van De Water, T.R.L-n-acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope, 2001, 111(7), 1147-1155.
90. Tozawa, K.; Okamoto, T.; Hayashi, Y.; Sasaki, S.; Kawai, N.; Kohri, K.N-acetyl-L-cysteine enhances chemotherapeutic effect on prostate cancer cells. Urol. Res., 2002, 30(1), 53-58.
91. Sasaki, M.; Kobayashi, D.; Watanabe, N.Augmented adriamycin sensitivity in cells transduced with an antisense tumor necrosis factor gene is mediated by caspase-3 downstream from reactive oxygen species. Jpn. J. Cancer Res., 2001, 92(9), 983-988.
92. Cort, A.; Ozdemir, E.; Timur, M.; Ozben, T.Effects of N-acetyl-lcysteine on bleomycin induced oxidative stress in malignant testicular germ cell tumors. Biochimie., 2012, 94(12), 2734-2739.
93. Cort, A.; Timur, M.; Dursun, E.; Kucuksayan, E.; Aslan, M.; Ozben, T.Effects of N-acetylcystein on bleomycin-induced apoptosis in malignant testicular germ cell tumors. J. Physiol. Biochem., 2012, 68(4), 555-562.
94. Traverso, N.; Ricciarelli, R.; Nitti, M.; Marengo, B.; Furfaro, A.L.; Pronzato, M.A.; Marinari, U.M.; Domenicotti, C.Role of glutathione in cancer progression and chemoresistance. Oxid. Med. Cell Longev., 2013, 2013(972913).
95. Akan, I.; Akan, S.; Akca, H.; Savas, B.; Ozben, T.N-acetylcysteine enhances multidrug resistance-associated protein 1 mediated doxorubicin resistance. Eur. J. Clin. Invest., 2004, 34(10), 683-689.
96. Akan, I.; Akan, S.; Akca, H.; Savas, B.; Ozben, T.Multidrug resistance-associated protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine sulfoximine. Cancer Cell Int., 2005, 5(1), 22.
97. Fruehauf, J.P.; Meyskens, F.L., Jr.Reactive oxygen species: a breath of life or death? Clin. Cancer Res., 2007; 13(3), 789-794.
98. Lu, J.; Chew, E.H.; Holmgren, A.Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc. Natl. Acad. Sci. U S A., 2007, 104(30), 12288-12293.
99. Maeda, H.; Hori, S.; Ohizumi, H.; Segawa, T.; Kakehi, Y.; Ogawa, O.; Kakizuka, A.Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine. Cell Death Differ., 2004, 11(7), 737-746.
100. [100] Block, K.I.; Koch, A.C.; Mead, M.N.; Tothy, P.K.; Newman, R.A.; Gyllenhaal, C.Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat. Rev., 2007, 33(5), 407-418.
101. [101] Block, K.I.; Koch, A.C.; Mead, M.N.; Tothy, P.K.; Newman, R.A.; Gyllenhaal, C.Impact of antioxidant supplementation on chemotherapeutic toxicity: a systematic review of the evidence from randomized controlled trials. Int. J. Cancer, 2008, 123(6), 1227-1239.
102. [102] Roomi, M.W.; 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(251-264).
103. [103] Roomi, M.W.; Roomi, N.W.; 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), R291-295.
104. [104] Harakeh, S.; Abdel-Massih, R.M.; Gil, P.R.; Sperling, R.A.; Meinhardt, A.; Niedwiecki, A.; Rath, M.; Parak, W.J.; Baydoun, E.The effect of PEG-coated gold nanoparticles on the antiproliferative potential of Specific Nutrient Synergy. Nanotoxicology, 2010, 4(2), 177-185.
105. [105] 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 T-cells. Leuk. Res., 2006, 30(7), 869-881.
106. [106] Roomi, M.W.; 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, 20(1), 25-32.
107. [107] Roomi, M.W.; Roomi, N.W.; 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, 32(2), 84-91.
108. [108] Mukhtar, H.; Ahmad, N.Cancer chemoprevention: future holds in multiple agents. Toxicol. Appl. Pharmacol., 1999, 158(3), 207-210.