NATURAL ANTIOXIDANTS AS DEFENSE SYSTEM AGAINST CANCER
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i5.24119Keywords:
Antioxidants, Cancer, Reactive oxygen species, Glutathione, Flavonoids, TumorAbstract
In living cells, the production of free radicals that comprise both reactive oxygen species (ROS) and reactive nitrogen species is highly regulated that help the cells to sustain redox homeostasis. Overproduction of ROS from mitochondrial electron transport chain leakage or excessive stimulation of xanthine oxidase and other oxidative enzymes leads to the uncontrolled production of free radicals leading to oxidative stress that can mediate damage to cell structures. This damage can be repaired by the antioxidant defense system. Antioxidants are capable of stabilizing, or deactivating, free radicals before they attack cellular components such as DNA, proteins, and lipids. The use of antioxidants in cancer prevention is a rapidly evolving research area where antioxidants scavenge free radicals and thus, indirectly help in the prevention of cancer. A wide range of antioxidants such as glutathione, N-acetylcysteine, coenzyme Q10, lycopene, flavonoids, and isoflavones when used in combination with chemotherapy and radiotherapy, result in the reduction of drug toxicity and enhanced efficacy of anticancer agents. This review aims at the use of these exogenous antioxidants as disease-oriented therapy and elucidating the relation of antioxidant enzymes with different types of cancers to overcome the harmful effects of cancer treatment.
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References
Gilbert DL. Oxygen and Living Processes: An Interdisciplinary Approach. New York: Springer; 1981.
Sireesha K, Rao SP. Oxidative stress and diabetes: An overview. Asian J Pharm Clin Res 2015;8:15-19.
Weidinger A, Kozlov AV. Biological activities of reactive oxygen and nitrogen species: Oxidative stress versus signal transduction. Biomolecules 2015;5:472-84.
Halliwell B. Free radicals, antioxidants, and human disease: Curiosity, cause, or consequence. Lancet 1994;344:721-724.
Yoshikawa T, Toyokuni S, Yamamoto Y, Naito Y. Free Radicals in Chemistry Biology and Medicine. London: OICA International; 2000.
Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem 2004;266:37-56.
Inoue M, Sato EF, Nishikawa M, Park AM, Kira Y, Imada I, et al. Mitochondrial generation of reactive oxygen species and its role in aerobic life. Curr Med Chem 2003;10:2495-505.
Cadenas E, Davies KJA. Mitochondrial free radical generation, oxidative stress, and aging. Free Rad Biol Med 2000;29:222-230.
Dupont GP, Huecksteadt TP, Marshall BC, Ryan US, Michael JR, Hoidal JR, et al. Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells. J Clin Invest 1992;89:197-202.
Shah K, Kumar RG, Verma S, Dubey RS. Effect of cadmium on lipid peroxidation, superoxide anion generationand activities of antioxidant enzymes in growing rice seedlings. Plant Sci 2001;6:1135-44.
Mittler R. Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci 2002;7:405-10.
Harman D. Ageing: A theory based on free radical and radiation chemistry. J Gerontol 1958;11:298-300.
Halliwell B, Gutteridge JM. Free Radicals in Biology and Medicine. Oxford: Oxford University Press; 1997.
Datta K, Sinha S, Chattopadhyay P. Reactive oxygen species in health and disease. Natl Med J India 2000;13:304-10.
Faraci FM, Didion SP. Vascular protection: Superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 2004;24:1367-73.
Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfi de/glutathione couple. Free Radic Biol Med 2001;30:1191-336.
Lander HM. An essential role for free radicals and derived species in signal transduction. FASEB J 1997;11:118-24.
Johnson IT, Williamson G, Musk SR. Anti carcinogenic factors in plant foods: A new class of nutrients? Nutr Res Rev 1994;7:175-204.
Mates JM, Gomez PC, De Castro IN. Antioxidant enzymes and human diseases. Clin Biochem 1999;32:595-603.
Lamson DW, Brignall MS. Antioxidants in cancer therapy; Their actions and interactions with oncologic therapies. Altern Med Rev 1999;4:304-29.
Prasad KN, Cole WC, Kumar B, Prasad KC. Scientific rationale for using high-dose multiple micronutrients as an adjunct to standard and experimental cancer therapies. J Am Coll Nutr 2001;20:450S-463S.
Forman HJ, Fukuto JM, Miller T, Zhang H, Rinna A, Levy S, et al. The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal. Arch Biochem Biophys 2008;477:183-95.
Alexandre J, Trachootham D, Huang P. Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat Rev Drug Discov 2009;8:579-91.
Stief TW. The physiology and pharmacology of singlet oxygen. Med Hypotheses 2003;60:567-72.
Palmer RM, Rees DD, Ashton DS, Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 1988;153:1251-6.
Halliwell B. Antioxidants and human disease: A general introduction. Nutr Rev 1997;55:S44-9.
Miljkovic D, Trajkovic V. Inducible nitric oxide synthase activation by interleukin-17. Cytokine Growth Factor Rev 2004;15:21-32.
Obermeier MT, White RE, Yang CS. Effects of bioflavonoids on hepatic P450 activities. Xenobiotica 1995;25:575-84.
McMillan K, Bredt DS, Hirsch DJ, Snyder SH, Clark JE, Masters BS, et al. Cloned, expressed rat cerebellar nitric oxide synthase contains stoichiometric amounts of heme, which binds carbon monoxide. Proc Natl Acad Sci U S A 1992;89:11141-5.
Park JS, Jung JS, Jeong YH, Hyun JW, Le TK, Kim DH, et al. Antioxidant mechanism of isoflavone metabolites in hydrogen peroxide-stimulated rat primary astrocytes: Critical role of hemeoxygenase-1 and NQO1 expression. J Neurochem 2011;119:909-19.
Carr AC, McCall MR, Frei B. Oxidation of LDL by myeloperoxidase and reactive nitrogen species: Reaction pathways and antioxidant protection. Arterioscler Thromb Vasc Biol 2000;20:1716-23.
Stamler JS, Jaraki O, Osborne J, Simon DI, Keaney J, Vita J, et al. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci U S A 1992;89:7674-7.
Bravo L. Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998;56:317-33.
Lomaestro BM, Malone M. Glutathione in health and disease: Pharmacotherapeutic issues. Ann Pharmacother 1995;29:1263-73.
Leonard SS, Harris GK, Shi XL. Metal-induced oxidative stress and signal transduction. Free Radic Biol Med 2004;37:1921-42.
Ercal N, Orhan GH, Burns AY. Toxic metals and oxidative stress Part 1: Mechanisms involved in metal induced oxidative damage. Curr Top Med Chem 2001;1:529-539.
Stepnik M, Stanczyk M, Arkusz J, Lewinska D. Assessment of apoptosis in thymocytes and splenocytes from mice exposed to arsenate in drinking water: Cytotoxic effects of arsenate on the cells in vitro. J Environ Sci Health Tox Hazard Subst Environ Eng 2005;40:369-384.
Sharma A, Sharma MK, Kumar M. Modulatory role of Emblica officinalis fruit extract against arsenic induced oxidative stress in Swiss albino mice. Chem Biol Interact 2009;180:20-30.
Gupta R, Flora SJ. Effect of Centella asiatica on arsenic induced oxidative stress and metal distribution in rats. J Appl Toxicol 2006;26:213-222.
Cuypers A, Vangronsveld J, Clijsters H. The chemical behaviors of heavy metals play prominent role in the induction of oxidative stress. Free Radic Res 199;31:39-43.
Rice-Evans CA, Diplock AT. Current status of antioxidant therapy. Free Radic Biol Med 1993;15:77-96.
Krinsky NI. Mechanism of action of biological antioxidants. Proc Soc Exp Biol Med 1992;200:248-254.
Bredt DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A 1990;87:682-5.
Amir Aslani B, Ghobadi S. Studies on oxidants and antioxidants with a brief glance at their relevance to the immune system. Life Sci 2016;146:163-73.
Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interv Aging 2007;2:219-36.
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 2006;160:1-40.
Dickinson DA, Forman HJ. Cellular glutathione and thiols metabolism. Biochem Pharmacol 2002;64:1019-26.
Gathwala G, Aggarwal R. Selenium supplementation for the pre-term Indian neonate. Indian J Public Health 2016;60:142-144.
Forsberg L, de Faire U, Morgenstern R. Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys 2001;389:84-93.
Jan AT, Azam M, Siddiqui K, Ali A, Choi I, Haq QM, et al. Heavy metals and human health: Mechanistic insight into toxicity and counter defense system of antioxidants. Int J Mol Sci 2015;16:29592-630.
Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol 2001;54:176-86.
Halliwell B, Gutteridge JM. Free Radicals in Biology and Medicine. 5th ed. Oxford: Oxford University Press; 2005. p. 753.
Duggett NA, Griffiths LA, McKenna OE, de Santis V, Yongsanguanchai N, Mokori EB, et al. Oxidative stress in the development, maintenance and resolution of paclitaxel-induced painful neuropathy. Neuroscience 2016;333:13-26.
Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cell. Chem Biol 2008;15:234-45.
Cao JY, Dixon SJ. Mechanisms of ferroptosis. Cell Mol Life Sci 2016;73:2195-209.
Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 2014;156:317-31.
Seiler A, Schneider M, Förster H, Roth S, Wirth EK, Culmsee C, et al. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 2008;8:237-48
Wang W, Xia MX, Chen J, Yuan R, Deng FN, Shen FF. Gene expression characteristics and regulation mechanisms of superoxide dismutase and its physiological roles in plants under stress. Biochemistry 2016;81:465-480.
Noor R, Mittal S, Iqbal J. Superoxide dismutase – Applications and relevance to human diseases. Med Sci Monit 2002;8:RA210-5.
Guo Z, Boekhoudt GH, Boss JM. Role of the intronic enhancer in tumor necrosis factor-mediated induction of manganous superoxide dismutase. J Biol Chem 2003;278:23570-8.
Borras C, Gambini J, Cabrera GM, Sastre J, Pallardo FV, Mann GE, et al. 17beta-oestradiol up-regulates longevity related, antioxidant enzyme expression via the ERK1 and ERK2 [MAPK]/NF kappa B cascade. Aging Cell 2005;4:113-118.
Pourvali K, Abbasi M, Mottaghi A. Role of superoxide dismutase 2 gene ala16Val polymorphism and total antioxidant capacity in diabetes and its complications. Avicenna J Med Biotechnol 2016;8:48-56.
Sjoquist PO, Marklund SL. Endothelium bound extracellular superoxide dismutase type C reduces damage in reperfuse dischaemic rat hearts. Cardiovasc Res 1992;26:347-50.
Leite PF, Danilovic A, Moriel P, Dantas K, Marklund S, Dantas AP, et al. Sustained decrease in superoxide dismutase activity underlies constrictive remodeling after balloon injury in rabbits. Arterioscler Thromb Vasc Biol 2003;23:2197-202.
Youn HD, Kim EJ, Roe JH, Hah YC, Kang SO. A novel nickel-containing superoxide dismutase from Streptomyces spp. Biochem J 1996;318:889-896.
Schmidt A, Gube M, Schmidt A, Kothe E. In silico analysis of nickel containing superoxide dismutase evolution and regulation. J Basic Microbiol 2009;49:109-18.
Ayeleso A, Brooks N, Oguntibeju O. Modulation of antioxidant status in streptozotocin-induced diabetic male wistar rats following intake of red palm oil and/or rooibos. Asian Pac J Trop Med 2014;7:536-44.
Edem DO. Haematological and histological alterations induced in rats by palm oil-containing diets. Eur J Sci Res 2009;32:405-518.
Iswaldi I, Arráez-Román D, RodrÃguez-Medina I, Beltrán-Debón R, Joven J, Segura-Carretero A, et al. Identification of phenolic compounds in aqueous and ethanolic rooibos extracts (Aspalathus linearis) by HPLC-ESI-MS (TOF/IT). Anal Bioanal Chem 2011;400:3643-54.
Masella R, Di Benedetto R, Vari R. Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. J Nutr Biochem 2005;16:577-86.
Ames BN, Shigenaga MK. Oxidants are a major contributor to aging. Ann N Y Acad Sci 1992;663:85-96.
Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants and degenerative diseases of aging. Proc Natl Acad Sci 1993;90:7915-22.
Zhou Y, Lee AS. Mechanism for the suppression of the mammalian stress response by genistein, an anticancer phytoestrogen from soy. J Natl Cancer Inst 1998;90:381-8.
Halliwell B, Aruoma OI. DNA and Free Radicals. Boca Raton: CRC Press; 1993.
Gupta S. Molecular steps of TNF receptor-mediated apoptosis. Curr Mol Med 2001;1:299-306.
Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 1991;51:794-8.
Kawanishi S, Hiraku Y, Pinlaor S, Ma N. Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis. Biol Chem 2006;387:365-72.
Seifirad S, Keshavarz A, Taslimi S, Aran S, Abbasi H, Ghaffari A, et al. Effect of pirfenidone on pulmonary fibrosis due to paraquat poisoning in rats. Clin Toxicol (Phila) 2012;50:754-8.
Lu LY, Ou N, Lu QB. Antioxidant induces DNA damage, cell death and mutagenicity in human lung and skin normal cells. Sci Rep 2013;3:3169.
Seifirad S, Masoudkabir F. Apelin could reduce risk of contrast-induced nephropathy in patients with congestive heart failure. Med Hypotheses 2013;81:898-900.
Weel EA, Redekop WK, Weening RS. Increased risk of malignancy for patients with chronic granulomatous disease and its possible link to the pathogenesis of cancer. Eur J Cancer 1996;32A:734-5.
Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, et al. Mitogenic signaling mediated by oxidants in ras-transformed fibroblasts. Science 1997;275:1649-52.
Rodrigues MS, Reddy MM, Sattler M. Cell cycle regulation by oncogenic tyrosine kinases in myeloid neoplasias: From molecular redox mechanisms to health implications. Antioxid Redox Signal 2008;10:1813-48.
Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene 2006;25:4647-62.
Coia LR, Moyland DJ. Introduction to Clinical Radiation Oncology. Madison, WI: Medical Physics Publishing; 1998. p. 15-9.
Galadari S, Rahman A, Pallichankandy S, Thayyullathil F. Reactive oxygen species and cancer paradox: To promote or to suppress? Free Radic Biol Med 2017;104:144-64.
Muthukkaruppan VR, Kubai L, Auerbach R. Tumor-induced neovascularization in the mouse eye. J Natl Cancer Inst 1982;69:699-708.
Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis. Cell 2011;146:873-87.
Nussbaumer S, Bonnabry P, Veuthey JL, Fleury-Souverain S. Analysis of anticancer drugs: A review. Talanta 2011;85:2265-89.
Gupta M, Dahiya J, Marwaha RK, Dureja H. Therapies in Cancer treatment: An overview. Int J Pharm Pharm Sci 2015;7:1-9.
Monsuez JJ, Charniot JC, Vignat N, Artigou JY. Cardiac side-effects of cancer chemotherapy. Int J Cardiol 2010;144:3-15.
Dropcho EJ. The neurologic side effects of chemotherapeutic agents. Continuum (Minneap Minn) 2011;17:95-112.
Kasapović J, Pejić S, Todorović A, Stojiljković V, Pajović SB. Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages. Cell Biochem Funct 2008;26:723-30.
Martin RC, Liu Q, Wo JM, Ray MB, Li Y. Chemoprevention of carcinogenic progression to esophageal adenocarcinoma by the manganese superoxide dismutase supplementation. Clin Cancer Res 2007;13:5176-82.
Fu TY, Hou YY, Chu ST, Liu CF, Huang CH, Chen HC, et al. Manganese superoxide dismutase and glutathione peroxidase as prognostic markers in patients with buccal mucosal squamous cell carcinomas. Head Neck 2011;33:1606-15.
Chung-man Ho J, Zheng S, Comhair SA, Farver C, Erzurum SC. Differential expression of manganese superoxide dismutase and catalase in lung cancer. Cancer Res 2001;61:8578-85.
Surapaneni KM, Sadagopan C. Status of lipid peroxidation and antioxidant enzymes in patients with carcinoma of breast. J Med Sci Res 2007;1:21-4.
Moscow JA, Schmidt L, Ingram DT, Gnarra J, Johnson B, Cowan KH, et al. Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer. Carcinogenesis 1994;15:2769-73.
Ratnasinghe D, Tangrea JA, Andersen MR, Barrett MJ, Virtamo J, Taylor PR, et al. Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res 2000;60:6381-3.
Tripathi P, Singh A. Natural resources from plants in the treatment of cancer: An update. Asian J Pharm Clin Res 2017;10:13-22.
Neuhouser ML. Dietary flavonoids and cancer risk: Evidence from human population studies. Nutr Cancer 2004;50:1-7.
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.
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;62:1025-35.
Le Marchand L, Murphy SP, Hankin JH, Wilkens LR, Kolonel LN. Intake of flavonoids and lung cancer. J Natl Cancer Inst 2000;92:154-60.
Thakur RS, Ahirwar B. Evaluation of medicinal plants for cytotoxicity against various cancer cell lines. Int J Pharm Pharm Sci 2017;9:198-202.
Bram S, Froussard P, Guichard M, Jasmin C, Augery Y, Sinoussi-Barre F, et al. Vitamin C preferential toxicity for malignant melanoma cells. Nature 1980;284:629-31.
Farooqui M, Pardeshi R, Jadhav S. Antioxidant-vitamin C: Lung function; Lung cancer. Asian J Pharm Clin Res 2016;9:43-51.
Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A 2005;102:13604-9.
Leung PY, Miyashita K, Young M, Tsao CS. Cytotoxic effect of ascorbate and its derivatives on cultured malignant and nonmalignant cell lines. Anticancer Res 1993;13:475-80.
Cameron E, Pauling L. The orthomolecular treatment of cancer. I. The role of ascorbic acid in host resistance. Chem Biol Interact 1974;9:273-83.
Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 1976;73:3685-9.
Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M, et al. Intravenously administered vitamin C as cancer therapy: Three cases. CMAJ 2006;174:937-42.
Benabadji SH, Wen R, Zheng JB, Dong XC, Yuan SG. Anticarcinogenic and antioxidant activity of diindolylmethane derivatives. Acta Pharmacol Sin 2004;25:666-71.
Exner M, Hermann M, Hofbauer R, Kapiotis S, Quehenberger P, Speiser W, et al. Genistein prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein. Free Radic Res 2001;34:101-12.
Fan S, Meng Q, Saha T, Sarkar FH, Rosen EM. Low concentrations of diindolylmethane, a metabolite of indole-3-carbinol, protect against oxidative stress in a BRCA1-dependent manner. Cancer Res 2009;69:6083-91.
Patel RP, Boersma BJ, Crawford JH, Hogg N, Kirk M, Kalyanaraman B, et al. Antioxidant mechanisms of isoflavones in lipid systems: Paradoxical effects of peroxyl radical scavenging. Free Radic Biol Med 2001;31:1570-81.
Chinni SR, Li Y, Upadhyay S, Koppolu PK, Sarkar FH. Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene 2001;20:2927-36.
Davis JN, Kucuk O, Djuric Z, Sarkar FH. Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes. Free Radic Biol Med 2001;30:1293-302.
Alhasan SA, Pietrasczkiwicz H, Alonso MD, Ensley J, Sarkar FH. Genistein-induced cell cycle arrest and apoptosis in a head and neck squamous cell carcinoma cell line. Nutr Cancer 1999;34:12-9.
Li Y, Bhuiyan M, Sarkar FH. Induction of apoptosis and inhibition of c-erbB-2 in MDA-MB-435 cells by genistein. Int J Oncol 1999;15:525-33.
Li Y, Ahmed F, Ali S, Philip PA, Kucuk O, Sarkar FH, et al. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res 2005;65:6934-42.
Lian F, Bhuiyan M, Li YW, Wall N, Kraut M, Sarkar FH, et al. Genistein-induced G2-M arrest, p21WAF1 upregulation, and apoptosis in a non-small-cell lung cancer cell line. Nutr Cancer 1998;31:184-91.
Zhou BB, Elledge SJ. The DNA damage response: Putting checkpoints in perspective. Nature 2000;408:433-9.
VandeCreek L, Rogers E, Lester J. Use of alternative therapies among breast cancer outpatients compared with the general population. Altern Ther Health Med 1999;5:71-6.
Oberley TD, Oberley LW. Antioxidant enzyme levels in cancer. Histol Histopathol 1997;12:525-35.
Dasari S, Wudayagiri R, Valluru L. Efficacy of treatment on antioxidant status in cervical cancer patients: A case control study. Free Radic Antioxid 2013;3:87-92.
Borek C. Dietary antioxidants and human cancer. Integr Cancer Ther 2004;3:333-41.
Sözen S, Coskun U, Sancak B, Bukan N, Günel N, Tunc L, et al. Serum levels of interleukin-18 and nitrite+nitrate in renal cell carcinoma patients with different tumor stage and grade. Neoplasma 2004;51:25-9.
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