Oxidative Stress: Harms and Benefits for Human Health

Gabriele Pizzino, Natasha Irrera, Mariapaola Cucinotta, Giovanni Pallio, Federica Mannino, Vincenzo Arcoraci, Francesco Squadrito, Domenica Altavilla, Alessandra Bitto, Gabriele Pizzino, Natasha Irrera, Mariapaola Cucinotta, Giovanni Pallio, Federica Mannino, Vincenzo Arcoraci, Francesco Squadrito, Domenica Altavilla, Alessandra Bitto

Abstract

Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues and the ability of a biological system to detoxify these reactive products. ROS can play, and in fact they do it, several physiological roles (i.e., cell signaling), and they are normally generated as by-products of oxygen metabolism; despite this, environmental stressors (i.e., UV, ionizing radiations, pollutants, and heavy metals) and xenobiotics (i.e., antiblastic drugs) contribute to greatly increase ROS production, therefore causing the imbalance that leads to cell and tissue damage (oxidative stress). Several antioxidants have been exploited in recent years for their actual or supposed beneficial effect against oxidative stress, such as vitamin E, flavonoids, and polyphenols. While we tend to describe oxidative stress just as harmful for human body, it is true as well that it is exploited as a therapeutic approach to treat clinical conditions such as cancer, with a certain degree of clinical success. In this review, we will describe the most recent findings in the oxidative stress field, highlighting both its bad and good sides for human health.

References

    1. Sato H., Shibata H., Shimizu T., Shibata S., Toriumi H., Ebine T. Differential cellular localization of antioxidant enzymes in the trigeminal ganglion. Neuroscience. 2013;248:345–358. doi: 10.1016/j.neuroscience.2013.06.010.
    1. Navarro-Yepes J., Zavala-Flores L., Anandhan A., Wang F., Skotak M., Chandra N. Antioxidant gene therapy against neuronal cell death. Pharmacology & Therapeutics. 2014;142:206–230. doi: 10.1016/j.pharmthera.2013.12.007.
    1. Rajendran P., Nandakumar N., Rengarajan T., Palaniswami R., Gnanadhas E. N., Lakshminarasaiah U. Antioxidants and human diseases. Clinica Chimica Acta. 2014;436:332–347. doi: 10.1016/j.cca.2014.06.004.
    1. Wu J. Q., Kosten T. R., Zhang X. Y. Free radicals, antioxidant defense system, and schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2013;46:200–206. doi: 10.1016/j.pnpbp.2013.02.015.
    1. Taniyama Y., Griendling K. K. Reactive oxygen species in the vasculature. Hypertension. 2003;42:1075–1081. doi: 10.1161/01.HYP.0000100443.09293.4F.
    1. Al-Gubory K. H., Garrel C., Faure P., Sugino N. Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress. Reproductive Biomedicine Online. 2012;25:551–560. doi: 10.1016/j.rbmo.2012.08.004.
    1. Hansen J. M., Go Y. M., Jones D. P. Nuclear and mitochondrial compartmentation of oxidative stress and redox signalling. Annual Review of Pharmacology and Toxicology. 2006;46:215–234. doi: 10.1146/annurev.pharmtox.46.120604.141122.
    1. Glasauer A., Chandel N. S. Targeting antioxidants for cancer therapy. Biochemical Pharmacology. 2014;92:90–101. doi: 10.1016/j.bcp.2014.07.017.
    1. Deponte M. Glutathione catalysis and the reaction mechanism of glutathione-dependent enzymes. Biochimica et Biophysica Acta. 1830;2013:3217–3266. doi: 10.1016/j.bbagen.2012.09.018.
    1. Halliwell B., Gutteridge J. M. C. Free Radicals in Biology and Medicine. 4th. Oxford, UK: Clarendon Press; 2007.
    1. Bahorun T., Soobrattee M. A., Luximon-Ramma V., Aruoma O. I. Free radicals and antioxidants in cardiovascular health and disease. Internet Journal of Medical Update. 2006;1:1–17.
    1. Kumar S., Pandey A. K. Free radicals: health implications and their mitigation by herbals. British Journal of Medicine and Medical Research. 2015;7:438–457.
    1. Kumar S., Pandey A. K. Chemistry and biological activities of flavonoids: an overview. The Scientific World Journal. 2013;2013:16. doi: 10.1155/2013/162750.162750
    1. Valko M., Izakovic M., Mazur M., Rhodes C. J., Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Molecular and Cellular Biochemistry. 2004;266:37–56.
    1. Valko M., Leibfritz D., Moncola J., Cronin M. D., Mazur M., Telser J. Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell Biology. 2007;39:44–84. doi: 10.1016/j.biocel.2006.07.001.
    1. Droge W. Free radicals in the physiological control of cell function. Physiological Reviews. 2002;82:47–95. doi: 10.1152/physrev.00018.2001.
    1. Willcox J. K., Ash S. L., Catignani G. L. Antioxidants and prevention of chronic disease. Critical Reviews in Food Science and Nutrition. 2004;44:275–295. doi: 10.1080/10408690490468489.
    1. Pacher P., Beckman J. S., Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiological Reviews. 2007;87:315–424. doi: 10.1152/physrev.00029.2006.
    1. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cellular Signalling. 2007;19:1807–1819. doi: 10.1016/j.cellsig.2007.04.009.
    1. Halliwell B. Biochemistry of oxidative stress. Biochemical Society Transactions. 2007;35:1147–1150. doi: 10.1042/BST0351147.
    1. Young I., Woodside J. Antioxidants in health and disease. Journal of Clinical Pathology. 2001;54:176–186.
    1. Valko M., Rhodes C. J., Moncol J., Izakovic M., Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chemico-Biological Interactions. 2006;160:1–40. doi: 10.1016/j.cbi.2005.12.009.
    1. Valko M., Morris H., Cronin M. T. D. Metals, toxicity and oxidative stress. Current Medicinal Chemistry. 2005;12:1161–1208.
    1. Parthasarathy S., Santanam N., Ramachandran S., Meilhac O. Oxidants and antioxidants in atherogenesis: an appraisal. Journal of Lipid Research. 1999;40:2143–2157.
    1. Frei B. Reactive Oxygen Species and Antioxidant Vitamins. Oregon State University: Linus Pauling Institute; 1997. .
    1. Nishida N., Arizumi T., Takita M., et al. Reactive oxygen species induce epigenetic instability through the formation of 8-hydroxydeoxyguanosine in human hepatocarcinogenesis. Digestive Diseases. 2013;31(5-6):459–466. doi: 10.1159/000355245.
    1. Yasui M., Kanemaru Y., Kamoshita N., Suzuki T., Arakawa T., Honma M. Tracing the fates of site-specifically introduced DNA adducts in the human genome. DNA Repair (Amst) 2014;15:11–20. doi: 10.1016/j.dnarep.2014.01.003.
    1. Valavanidis A., Vlachogianni T., Fiotakis K., Loridas S. Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms. International Journal of Environmental Research and Public Health. 2013;10(9):3886–3907. doi: 10.3390/ijerph10093886.
    1. Pizzino G., Bitto A., Interdonato M., et al. Oxidative stress and DNA repair and detoxification gene expression in adolescents exposed to heavy metals living in the Milazzo-Valle del Mela area (Sicily, Italy) Redox Biology. 2014;2:686–693. doi: 10.1016/j.redox.2014.05.003.
    1. Chatterjee M., Saluja R., Kanneganti S., Chinta S., Dikshit M. Biochemical and molecular evaluation of neutrophil NOS in spontaneously hypertensive rats. Cellular and Molecular Biology. 2007;53:84–93.
    1. Ceriello A. Possible role of oxidative stress in the pathogenesis of hypertension. Diabetes Care. 2008;31(Supplement 2):S181–S184. doi: 10.2337/dc08-s245.
    1. Halliwell B. Role of free radicals in neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs & Aging. 2001;18:685–716.
    1. Singh R. P., Sharad S., Kapur S. Free radicals and oxidative stress in neurodegenerative diseases: relevance of dietary antioxidants. Journal, Indian Academy of Clinical Medicine. 2004;5:218–225.
    1. Christen Y. Oxidative stress and Alzheimer disease. The American Journal of Clinical Nutrition. 2000;71:621S–629S.
    1. Butterfield D. A. Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer’s disease brain. A review. Free Radical Research. 2002;36:1307–1313.
    1. Caramori G., Papi A. Oxidants and asthma. Thorax. 2004;59:170–173.
    1. Guo R. F., Ward P. A. Role of oxidants in lung injury during sepsis. Antioxidants & Redox Signaling. 2007;9:1991–2002. doi: 10.1089/ars.2007.1785.
    1. Hoshino Y., Mishima M. Antioxidants & redox signaling redox-based therapeutics for lung diseases. Antioxidants & Redox Signaling. 2008;10:701–704. doi: 10.1089/ars.2007.1961.
    1. MacNee W. Oxidative stress and lung inflammation in airways disease. European Journal of Pharmacology. 2001;429:195–207.
    1. Walston J., Xue Q., Semba R. D., et al. Serum antioxidants, inflammation, and total mortality in older women. American Journal of Epidemiology. 2006;163:18–26. doi: 10.1093/aje/kwj007.
    1. Mahajan A., Tandon V. R. Antioxidants and rheumatoid arthritis. Journal of Indian Rheumatology Association. 2004;12:139–142.
    1. Galle J. Oxidative stress in chronic renal failure. Nephrology, Dialysis, Transplantation. 2001;16:2135–2142.
    1. Sadeg N., Pham-Huy C., Martin C., Warnet J. M., Claude J. R. Effect of cyclosporin A and its metabolites and analogs on lipid peroxidation in rabbit renal microsomes. Drug and Chemical Toxicology. 1993;16:165–174. doi: 10.3109/01480549309031994.
    1. Massicot F., Martin C., Dutertre-Catella H., et al. Modulation of energy status and cytotoxicity induced by FK506 and cyclosporin A in a renal epithelial cell line. Archives of Toxicology. 1997;71:529–531.
    1. Massicot F., Lamouri A., Martin C., et al. Preventive effects of two PAF-antagonists, PMS 536 and PMS 549, on cyclosporin-induced LLC-PK1 oxidative injury. Journal of Lipid Mediators and Cell Signalling. 1997;15:203–214.
    1. Samuel J. B., Stanley J. A., Princess R. A., Shanthi P., Sebastian M. S. Gestational cadmium exposure-induced ovotoxicity delays puberty through oxidative stress and impaired steroid hormone levels. Journal of Medical Toxicology. 2011;7(3):195–204. doi: 10.1007/s13181-011-0143-9.
    1. Interdonato M., Pizzino G., Bitto A., et al. Cadmium delays puberty onset and testis growth in adolescents. Clinical Endocrinology. 2015;83(3):357–362. doi: 10.1111/cen.12704.
    1. Mene-Saffrane L., DellaPenna D. Biosynthesis, regulation and functions of tocochromanols in plants. Plant Physiology and Biochemistry. 2010;48:301–309. doi: 10.1016/j.plaphy.2009.11.004.
    1. Sheppard A., Pennington J. A. T., Weihrauch J. L. Analysis and distribution of vitamin E in vegetable oils and foods. In: Packer F. J., editor. Vitamin E in Health and Disease. New York: Marcel Dekker Inc; 1993. pp. 9–31.
    1. Sundl I., Murkovic M., Bandoniene D., Winklhofer-Roob B. M. Vitamin E content of foods: comparison of results obtained from food composition tables and HPLC analysis. Clinical Nutrition. 2007;26:145–153. doi: 10.1016/j.clnu.2006.06.003.
    1. Boscoboinik D., Szewczyk A., Hensey C., Azzi A. Inhibition of cell proliferation by alpha-tocopherol. Role of protein kinase C. The Journal of Biological Chemistry. 1991;266:6188–6194.
    1. Özer N. K., Palozza P., Boscoboinik D., Azzi A. D-Alpha-tocopherol inhibits low density lipoprotein induced proliferation and protein kinase C activity in vascular smooth muscle cells. FEBS Letters. 1993;322:307–310.
    1. Sirikci Ö., Özer N. K., Azzi A. Dietary cholesterol-induced changes of protein kinase C and the effect of vitamin E in rabbit aortic smooth muscle cells. Atherosclerosis. 1996;126:253–263.
    1. Özer N. K., Sirikci O., Taha S., San T., Moser U., Azzi A. Effect of vitamin E and probucol on dietary cholesterol-induced atherosclerosis in rabbits. Free Radical Biology & Medicine. 1998;24:226–233.
    1. Meydani M., Kwan P., Band M., et al. Long-term vitamin E supplementation reduces atherosclerosis and mortality in Ldlr−/− mice, but not when fed Western style diet. Atherosclerosis. 2014;233:196–205. doi: 10.1016/j.atherosclerosis.2013.12.006.
    1. Keaney J. F., Jr., Simon D. I., Freedman J. E. Vitamin E and vascular homeostasis: implications for atherosclerosis. The FASEB Journal. 1999;13:965–975.
    1. Febbraio M., Podrez E., Smith J., et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. Journal of Clinical Investigation. 2000;105:1049–1056. doi: 10.1172/JCI9259.
    1. Ozer N. K., Negis Y., Aytan N., et al. Vitamin E inhibits CD36 scavenger receptor expression in hypercholesterolemic rabbits. Atherosclerosis. 2006;184:15–20. doi: 10.1016/j.atherosclerosis.2005.03.050.
    1. Ricciarelli R., Zingg J. M., Azzi A. Vitamin E reduces the uptake of oxidized LDL by inhibiting CD36 scavenger receptor expression in cultured aortic smooth muscle cells. Circulation. 2000;102:82–87.
    1. Tang F., Lu M., Zhang S., et al. Vitamin E conditionally inhibits atherosclerosis in ApoE knockout mice by anti-oxidation and regulation of vasculature gene expressions. Lipids. 2014;49:1215–1223. doi: 10.1007/s11745-014-3962-z.
    1. Catalgol B., Ziaja I., Breusing N., et al. The proteasome is an integral part of solar ultraviolet a radiation-induced gene expression. The Journal of Biological Chemistry. 2009;284:30076–30086. doi: 10.1074/jbc.M109.044503.
    1. Hershko A., Ciechanover A. The ubiquitin system. Annual Review of Biochemistry. 1998;67:425–479. doi: 10.1146/annurev.biochem.67.1.425.
    1. Sozen E., Karademir B., Yazgan B., Bozaykut P., Ozer N. K. Potential role of proteasome on c-Jun related signaling in hypercholesterolemia induced atherosclerosis. Redox Biology. 2014;2:732–738. doi: 10.1016/j.redox.2014.02.007.
    1. Otero P., Bonet B., Herrera E., Rabano A. Development of atherosclerosis in the diabetic BALB/c mice. Prevention with vitamin E administration. Atherosclerosis. 2005;182:259–265. doi: 10.1016/j.atherosclerosis.2005.02.024.
    1. Huang Z. G., Liang C., Han S. F., Wu Z. G. Vitamin E ameliorates ox-LDL-induced foam cells formation through modulating the activities of oxidative stress-induced NF-kappaB pathway. Molecular and Cellular Biochemistry. 2012;363:11–19. doi: 10.1007/s11010-011-1153-2.
    1. Gaedicke S., Zhang X., Schmelzer C., et al. Vitamin E dependent microRNA regulation in rat liver. FEBS Letters. 2008;582:3542–3546. doi: 10.1016/j.febslet.2008.09.032.
    1. Barella L., Muller P. Y., Schlachter M., et al. Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats. Biochimica et Biophysica Acta. 2004;1689:66–74. doi: 10.1016/j.bbadis.2004.02.002.
    1. Podszun M. C., Grebenstein N., Spruss A., et al. Dietary alpha-tocopherol and atorvastatin reduce high-fat-induced lipid accumulation and down-regulate CD36 protein in the liver of guinea pigs. The Journal of Nutritional Biochemistry. 2014;25:573–579. doi: 10.1016/j.jnutbio.2014.01.008.
    1. Abdala-Valencia H., Berdnikovs S., Soveg F., Cook-Mills J. M. Alpha-tocopherol supplementation of allergic female mice inhibits development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2014;307:L482–L496. doi: 10.1152/ajplung.00132.2014.
    1. Abdala-Valencia H., Soveg F., Cook-Mills J. M. γ-Tocopherol supplementation of allergic female mice augments development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates. American Journal of Physiology - Lung Cellular and Molecular Physiology. 2016;310:L759–L771. doi: 10.1152/ajplung.00301.2015.
    1. Cook-Mills J. M., Avila P. C. Vitamin E and D regulation of allergic asthma immunopathogenesis. International Immunopharmacology. 2014;23:364–372. doi: 10.1016/j.intimp.2014.08.007.
    1. Marchese M. E., Kumar R., Colangelo L. A., et al. The vitamin E isoforms alpha-tocopherol and gamma-tocopherol have opposite associations with spirometric parameters: the CARDIA study. Respiratory Research. 2014;15:p. 31. doi: 10.1186/1465-9921-15-31.
    1. Cook-Mills J. M. Isoforms of vitamin E differentially regulate PKC alpha and inflammation: a review. Journal of Clinical & Cellular Immunology. 2013;4(137) doi: 10.4172/2155-9899.1000137.
    1. Cook-Mills J. M., Abdala-Valencia H., Hartert T. Two faces of vitamin e in the lung. American Journal of Respiratory and Critical Care Medicine. 2013;188:279–284. doi: 10.1164/rccm.201303-0503ED.
    1. Abdala-Valencia H., Berdnikovs S., Cook-Mills J. M. Vitamin E isoforms differentially regulate intercellular adhesion molecule-1 activation of PKCalpha in human microvascular endothelial cells. PLoS One. 2012;7, article e41054 doi: 10.1371/journal.pone.0041054.
    1. McCary C. A., Abdala-Valencia H., Berdnikovs S., Cook-Mills J. M. Supplemental and highly elevated tocopherol doses differentially regulate allergic inflammation: reversibility of alpha-tocopherol and gamma-tocopherol’s effects. Journal of Immunology. 2011;186:3674–3685. doi: 10.4049/jimmunol.1003037.
    1. Cook-Mills J. M., McCary C. A. Isoforms of vitamin E differentially regulate inflammation. Endocrine, Metabolic & Immune Disorders Drug Targets. 2010;10:348–366.
    1. Cook-Mills J. M., Marchese M. E., Abdala-Valencia H. Vascular cell adhesion molecule-1 expression and signaling during disease: regulation by reactive oxygen species and antioxidants. Antioxidants & Redox Signaling. 2011;15:1607–1638. doi: 10.1089/ars.2010.3522.
    1. Abdala-Valencia H., Cook-Mills J. M. VCAM-1 signals activate endothelial cell protein kinase Cα via oxidation. Journal of Immunology. 2006;177:6379–6387.
    1. Berdnikovs S., Abdala-Valencia H., McCary C., et al. Isoforms of vitamin E have opposing immunoregulatory funcitons during inflammation by regulating leukocyte recruitment. Journal of Immunology. 2009;182:4395–4405. doi: 10.4049/jimmunol.0803659.
    1. Cook-Mills J. M., Gebretsadik T., Abdala-Valencia H., et al. Brief research report: interaction of vitamin E isoforms on asthma and allergic airway disease. Thorax. 2016;71:954–956. doi: 10.1136/thoraxjnl-2016-208494.
    1. Wu D., Han S. N., Meydani M., Meydani S. N. Effect of concomitant consumption of fish oil and vitamin E on T cell mediated function in the elderly: a randomized double-blind trial. Journal of the American College of Nutrition. 2006;25:300–306.
    1. Christiani D. C., Ye T. T., Wegman D. H., Eisen E. A., Dai H. L., Lu P. L. Pulmonary function among cotton textile workers. A study of variability in symptom reporting, across-shift drop in FEV1, and longitudinal change. Chest. 1994;105:1713–1721.
    1. Jacobs R. R., Boehlecke B., van Hage-Hamsten M., Rylander R. Bronchial reactivity, atopy, and airway response to cotton dust. The American Review of Respiratory Disease. 1993;148:19–24. doi: 10.1164/ajrccm/148.1.19.
    1. Delfino R. J., Quintana P. J., Floro J., et al. Association of FEV1 in asthmatic children with personal and microenvironmental exposure to airborne particulate matter. Environmental Health Perspectives. 2004;112:932–941.
    1. Koskela H., Tukiainen H., Kononoff A., Pekkarinen H. Effect of whole-body exposure to cold and wind on lung function in asthmatic patients. Chest. 1994;105:1728–1731.
    1. Blanc P. D., Eisner M. D., Katz P. P., et al. Impact of the home indoor environment on adult asthma and rhinitis. Journal of Occupational and Environmental Medicine. 2005;47:362–372.
    1. Fedulov A. V., Kobzik L. Allergy risk is mediated by dendritic cells with congenital epigenetic changes. American Journal of Respiratory Cell and Molecular Biology. 2011;44:285–292. doi: 10.1165/rcmb.2009-0400OC.
    1. Lim R. H., Kobzik L. Maternal transmission of asthma risk. American Journal of Reproductive Immunology. 2009;61:1–10. doi: 10.1111/j.1600-0897.2008.00671.x.
    1. Langlet C., Springael C., Johnson J., et al. PKC-alpha controls MYD88-dependent TLR/IL-1R signaling and cytokine production in mouse and human dendritic cells. European Journal of Immunology. 2010;40:505–515. doi: 10.1002/eji.200939391.
    1. Cejas P. J., Carlson L. M., Zhang J., et al. Protein kinase C betaII plays an essential role in dendritic cell differentiation and autoregulates its own expression. The Journal of Biological Chemistry. 2005;280:28412–28423. doi: 10.1074/jbc.M500345200.
    1. Lin Y. F., Lee H. M., Leu S. J., Tsai Y. H. The essentiality of PKCalpha and PKCbetaI translocation for CD14+monocyte differentiation towards macrophages and dendritic cells, respectively. Journal of Cellular Biochemistry. 2007;102:429–441. doi: 10.1002/jcb.21305.
    1. Lin Y. F., Leu S. J., Huang H. M., Tsai Y. H. Selective activation of specific PKC isoforms dictating the fate of CD14(+) monocytes towards differentiation or apoptosis. Journal of Cellular Physiology. 2011;226:122–131. doi: 10.1002/jcp.22312.
    1. Asehnoune K., Strassheim D., Mitra S., Yeol Kim J., Abraham E. Involvement of PKCalpha/beta in TLR4 and TLR2 dependent activation of NF-kappaB. Cellular Signalling. 2005;17:385–394. doi: 10.1016/j.cellsig.2004.08.005.
    1. Ramadan G., Schmidt R. E., Schubert J. In vitro generation of human CD86+ dendritic cells from CD34+ haematopoietic progenitors by PMA and in serum-free medium. Clinical and Experimental Immunology. 2001;125:237–244.
    1. Davis T. A., Saini A. A., Blair P. J., et al. Phorbol esters induce differentiation of human CD34+ hemopoietic progenitors to dendritic cells: evidence for protein kinase C-mediated signaling. Journal of Immunology. 1998;160:3689–3697.
    1. Rajotte D., Haddad P., Haman A., Cragoe E. J., Jr., Hoang T. Role of protein kinase C and the Na+/H+ antiporter in suppression of apoptosis by granulocyte macrophage colony-stimulating factor and interleukin-3. The Journal of Biological Chemistry. 1992;267:9980–9987.
    1. Salh B., Hoeflick K., Kwan W., Pelech S. Granulocyte-macrophage colony-stimulating factor and interleukin-3 potentiate interferon-gamma-mediated endothelin production by human monocytes: role of protein kinase C. Immunology. 1998;95:473–479.
    1. St Louis D. C., Woodcock J. B., Franzoso G., et al. Evidence for distinct intracellular signaling pathways in CD34+ progenitor to dendritic cell differentiation from a human cell line model. Journal of Immunology. 1999;162:3237–3248.
    1. Cejas P. J., Carlson L. M., Kolonias D., et al. Regulation of RelB expression during the initiation of dendritic cell differentiation. Molecular and Cellular Biology. 2005;25:7900–7916. doi: 10.1128/MCB.25.17.7900-7916.2005.
    1. Farren M. R., Carlson L. M., Lee K. P. Tumor-mediated inhibition of dendritic cell differentiation is mediated by down regulation of protein kinase C beta II expression. Immunologic Research. 2010;46:165–176. doi: 10.1007/s12026-009-8118-5.
    1. Geijsen N., Spaargaren M., Raaijmakers J. A., Lammers J. W., Koenderman L., Coffer P. J. Association of RACK1 and PKCbeta with the common beta-chain of the IL-5/IL-3/GM-CSF receptor. Oncogene. 1999;18:5126–5130. doi: 10.1038/sj.onc.1202896.
    1. Verdelli D., Nobili L., Todoerti K., et al. Molecular targeting of the PKC-beta inhibitor enzastaurin (LY317615) in multiple myeloma involves a coordinated downregulation of MYC and IRF4 expression. Hematological Oncology. 2009;27:23–30. doi: 10.1002/hon.875.
    1. Hamdorf M., Berger A., Schule S., Reinhardt J., Flory E. PKCdelta-induced PU.1 phosphorylation promotes hematopoietic stem cell differentiation to dendritic cells. Stem Cells. 2011;29:297–306. doi: 10.1002/stem.564.
    1. Lee J. S., Kim I. S., Ryu J. S., Yun C. Y. House dust mite, Dermatophagoides pteronissinus increases expression of MCP-1, IL-6, and IL-8 in human monocytic THP-1 cells. Cytokine. 2008;42:365–371. doi: 10.1016/j.cyto.2008.03.010.
    1. Guler R., Afshar M., Arendse B., et al. PKCdelta regulates IL-12p40/p70 production by macrophages and dendritic cells, driving a type 1 healer phenotype in cutaneous leishmaniasis. European Journal of Immunology. 2011;41:706–715. doi: 10.1002/eji.201040985.
    1. McCary C. A., Yoon Y., Panagabko C., Cho W., Atkinson J., Cook-Mills J. M. Vitamin E isoforms directly bind PKCalpha and differentially regulate activation of PKCalpha. The Biochemical Journal. 2012;441:189–198. doi: 10.1042/BJ20111318.
    1. Mahomoodally M. F., Gurib-Fakim A., Subratty A. H. Antimicrobial activities and phytochemical profiles of endemic medicinal plants of Mauritius. Pharmaceutical Biology. 2005;43(3):237–242.
    1. Pandey A. K. Anti-staphylococcal activity of a pan-tropical aggressive and obnoxious weed Parihenium histerophorus: an in vitro study. National Academy Science Letters. 2007;30(11-12):383–386.
    1. Heim K. E., Tagliaferro A. R., Bobilya D. J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. Journal of Nutritional Biochemistry. 2002;13(10):572–584.
    1. Kumar S., Mishra A., Pandey A. K. Antioxidant mediated protective effect of Parthenium hysterophorus against oxidative damage using in vitro models. BMC Complementary and Alternative Medicine. 2013;13, article 120 doi: 10.1186/1472-6882-13-120.
    1. Kumar S., Pandey A. K. Phenolic content, reducing power and membrane protective activities of Solanum xanthocarpum root extracts. Vegetos-An International Journal of Plant Research. 2013;26:301–307. doi: 10.5958/j.2229-4473.26.1.043.
    1. Leopoldini M., Russo N., Chiodo S., Toscano M. Iron chelation by the powerful antioxidant flavonoid quercetin. Journal of Agricultural and Food Chemistry. 2006;54(17):6343–6351. doi: 10.1021/jf060986h.
    1. Kumar S., Gupta A., Pandey A. K. Calotropis procera root extract has capability to combat free radical mediated damage. ISRN Pharmacology. 2013;2013:8. doi: 10.1155/2013/691372.691372
    1. Cook N. C., Samman S. Review: flavonoids-chemistry, metabolism, cardioprotective effects and dietary sources. Journal of Nutritional Biochemistry. 1996;7(2):66–76.
    1. Rice-Evans C. A., Miller N. J., Bolwell P. G., Broamley P. M., Pridham J. B. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radical Research. 1995;22(4):375–383.
    1. Pandey A. K., Mishra A. K., Mishra A. Antifungal and antioxidative potential of oil and extracts derived from leaves of Indian spice plant Cinnamomum tamala. Cellular and Molecular Biology. 2012;58:142–147.
    1. Halliwell B., Gutteridge J. M. C. Free Radicals in Biology and Medicine. Oxford, UK: Oxford University Press; 1998.
    1. Mishra A., Kumar S., Pandey A. K. Scientific validation of the medicinal efficacy of Tinospora cordifolia. The Scientific World Journal. 2013;2013:8. doi: 10.1155/2013/292934.292934
    1. Ganai A. A., Khan A. A., Malik Z. A., Farooqi H. Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating d-galactosamine induced fulminant hepatic failure in Wistar rats. Toxicology and Applied Pharmacology. 2015;283:139–146. doi: 10.1016/j.taap.2015.01.012.
    1. Clarkson T. B., Anthony M. S., Morgan T. M. Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens. The Journal of Clinical Endocrinology and Metabolism. 2001;86:41–47. doi: 10.1210/jcem.86.1.7151.
    1. Adams M. R., Golden D. L., Williams J. K., Franke A. A., Register T. C., Kaplan J. R. Soy protein containing isoflavones reduces the size of atherosclerotic plaques without affecting coronary artery reactivity in adult male monkeys. The Journal of Nutrition. 2005;135:2852–2856.
    1. Yamakoshi J., Piskula M. K., Izumi T., et al. Isoflavone aglycone-rich extract without soy protein attenuates atherosclerosis development in cholesterol-fed rabbits. The Journal of Nutrition. 2000;130:1887–1893.
    1. Kanazawa T., Osanai T., Zhang X. S., et al. Protective effects of soy protein on the peroxidizability of lipoproteins in cerebrovascular diseases. The Journal of Nutrition. 1995;125:639S–646S.
    1. Tikkanen M. J., Wahala K., Ojala S., Vihma V., Adlercreutz H. Effect of soybean phytoestrogen intake on low density lipoprotein oxidation resistance. Proceedings of the National Academy of Sciences of the United States of America. 1998;95:3106–3110.
    1. Wiseman H., O’Reilly J. D., Adlercreutz H., et al. Isoflavone phytoestrogens consumed in soy decrease F(2)-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. The American Journal of Clinical Nutrition. 2000;72:395–400.
    1. Ryan-Borchers T. A., Park J. S., Chew B. P., McGuire M. K., Fournier L. R., Beerman K. A. Soy isoflavones modulate immune function in healthy postmenopausal women. The American Journal of Clinical Nutrition. 2006;83:1118–1125.
    1. Hodgson J. M., Puddey I. B., Croft K. D., Mori T. A., Rivera J., Beilin L. J. Isoflavonoids do not inhibit in vivo lipid peroxidation in subjects with high-normal blood pressure. Atherosclerosis. 1999;145:167–172.
    1. Samman S., Lyons Wall P. M., Chan G. S., Smith S. J., Petocz P. The effect of supplementation with isoflavones on plasma lipids and oxidisability of low density lipoprotein in premenopausal women. Atherosclerosis. 1999;147:277–283.
    1. Vega-Lopez S., Yeum K. J., Lecker J. L., et al. Plasma antioxidant capacity in response to diets high in soy or animal protein with or without isoflavones. The American Journal of Clinical Nutrition. 2005;81:43–49.
    1. Choi C., Cho H., Park J., Cho C., Song Y. Suppressive effects of genistein on oxidative stress and NFkappaB activation in RAW 264.7 macrophages. Bioscience, Biotechnology, and Biochemistry. 2003;67:1916–1922. doi: 10.1271/bbb.67.1916.
    1. Naidu K. A. Vitamin C in human health and disease is still a mystery? An overview. Nutrition Journal. 2003;2:p. 7. doi: 10.1186/1475-2891-2-7.
    1. Crott J. W., Fenech M. Effect of vitamin C supplementation on chromosome damage, apoptosis and necrosis ex vivo. Carcinogenesis. 1999;20(6):1035–1041.
    1. Carr A. C., Frei B. Does vitamin C act as pro-oxidant under physiological conditions? FASEB Journal. 1999;13:1007–1024.
    1. Suzuki K., Koike H., Matsui H., et al. Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3. International Journal of Cancer. 2002;99:846–852. doi: 10.1002/ijc.10428.
    1. Raschke M., Rowland I. R., Magee P. J., Pool-Zobel B. L. Genistein protects prostate cells against hydrogen peroxide-induced DNA damage and induces expression of genes involved in the defence against oxidative stress. Carcinogenesis. 2006;27:2322–2330. doi: 10.1093/carcin/bgl082.
    1. Takada Y., Mukhopadhyay A., Kundu G. C., Mahabeleshwar G. H., Singh S., Aggarwal B. B. Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein tyrosine kinase. Journal of Biological Chemistry. 2003;278(26):24233–24241. doi: 10.1074/jbc.M212389200.
    1. Harakeh S., Diab-Assaf M., Khalife J. C., et al. Ascorbic acid induces apoptosis in adult T-cell leukemia. Anticancer Research. 2007;27(1A):289–298.
    1. Nakano H., Nakajima A., Sakon-Komazawa S., Piao J. H., Xue X., Okumura K. Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death and Differentiation. 2006;13(5):730–777. doi: 10.1038/sj.cdd.4401830.
    1. Belin S., Kaya F., Duisit G., Giacometti S., Ciccolini J., Fontés M. Antiproliferative effect of ascorbic acid is associated with the inhibition of genes necessary to cell cycle progression. PLoS One. 2009;4(2) doi: 10.1371/journal.pone.0004409.
    1. Migliozzi J. A. Effect of ascorbic acid on tumour growth. British Journal of Cancer. 1977;35:p. 448.
    1. Kishino K., Hashimoto K., Amano O., Kochi M., Liu W., Sakagami H. Tumor-specific cytotoxicity and type of cell death induced by sodium 5,6-benzylidene-l-ascorbate. Anticancer Research. 2008;28:2577–2584.
    1. Chen Q., Espey M. G., Sun A. Y., et al. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proceedings of the National Academy of Science. 2008;105(32):11105–11109. doi: 10.1073/pnas.0804226105.
    1. Chen Q., Espey M. G., Sun A. Y., et al. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proceedings of the National Academy of Science. 2007;104(21):8749–8754. doi: 10.1073/pnas.0702854104.
    1. Richardson D. R., Ponka P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochimica et Biophysica Acta. 1997;1331(1):1–40.
    1. Hann H. W., Evans A. E., Siegel S. E., et al. Prognostic importance of serum ferritin in patients with stages III and IV neuroblastoma: the Children’s Cancer Study Group experience. Cancer Research. 1985;45(6):2843–2848.
    1. Shen L., Zhao H. Y., Du J., Wang F. Anti-tumor activities of four chelating agents against human neuroblastoma cells. In Vivo. 2005;19(1):233–236.
    1. Chen Q., Espey M. G., Krishna M. C., et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proceedings of the National Academy of Science. 2005;102(38):13604–13609. doi: 10.1073/pnas.0506390102.
    1. Bhat S. H., Azmi A. S., Hanif S., Hadi S. M. Ascorbic acid mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for anticancer properties. International Journal of Biochemistry and Cell Biology. 2006;38:2074–2081. doi: 10.1016/j.biocel.2006.05.017.
    1. Kinoshita N., Yamamura T., Teranuma H., et al. Interaction between dental metals and antioxidants assessed by cytotoxicity assay and ESR spectroscopy. Anticancer Research. 2002;22:4017–4022.
    1. Sakagami H., Arakawa H., Haeda M., et al. Production of hydrogen peroxide and methionine sulfoxide by epigallactocatechin gallate and antioxidants. Anticancer Research. 2001;21:2633–2642.
    1. Vojdani A., Bazargan M., Vojdani E., Wright J. New evidence for antioxidant properties of vitamin C. Cancer Detection and Prevention. 2000;24(6):508–523.
    1. Kelley E. E., Domann F. E., Buettner G. R., Oberley L. W., Patrick Burns C. Increased efficiency of in vitro Photofrin photosensitization of human oral squamous cell carcinoma by iron and ascorbate. Journal of Photochemistry and Photobiology B: Biology. 1997;40:273–277.
    1. Noto V., Taper H. S., Jiang Y.-H., Janssens J., Bonte J., De Loecker W. Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. 1. Synergism of combined vitamin C and K3 action. Cancer. 1989;63:901–906.
    1. Leveille C. R., Schwartz E. R. Effect of ascorbate on lysosomal enzyme activities in guinea pig cartilage and adrenals. International Journal for Vitamin and Nutrition Research. 1982;52:436–441.
    1. Harada T., Enomoto A., Kitazawa T., Maita K., Shirasu Y. Oral leukoplakia and costochondral hyperplasia induced by diethylnitrosamine in hamsters exposed to cigarette smoke with or without dietary vitamin C. Veterinary Pathology. 1987;24:p. 257. doi: 10.1177/030098588702400310.
    1. Prochazkova D., Bousova I., Wilhelmova N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia. 2011;82:513–523. doi: 10.1016/j.fitote.2011.01.018.
    1. Park E. J., Pezzuto J. M. Flavonoids in cancer prevention. Anti-Cancer Agents in Medicinal Chemistry. 2012;12:836–851.
    1. Hodnick W. F., Milosavljevic E. B., Nelson J. H., Pardini R. S. Electrochemistry of flavonoids. Relationships between redox potentials, inhibition of mitochondrial respiration, and production of oxygen radicals by flavonoids. Biochemical Pharmacology. 1988;37:2607–2611.
    1. Choi S. I., Jeong C. S., Cho S. Y., Lee Y. S. Mechanism of apoptosis induced by apigenin in HepG2 human hepatoma cells: involvement of reactive oxygen species generated by NADPH oxidase. Archives of Pharmacal Research. 2007;30:1328–1335.
    1. Lee Y. S. Role of NADPH oxidase-mediated generation of reactive oxygen species in the mechanism of apoptosis induced by phenolic acids in HepG2 human hepatoma cells. Archives of Pharmacal Research. 2005;28:1183–1189.
    1. Alhosin M., Leon-Gonzalez A. J., Dandache I., et al. Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway. Scientific Reports. 2015;5:p. 8996. doi: 10.1038/srep08996.
    1. Kim J. H., Auger C., Kurita I., et al. Aronia melanocarpa juice, a rich source of polyphenols, induces endothelium-dependent relaxations in porcine coronary arteries via the redox-sensitive activation of endothelial nitric oxide synthase. Nitric Oxide: Biology and Chemistry. 2013;35:54–64. doi: 10.1016/j.niox.2013.08.002.
    1. Sharif T., Stambouli M., Burrus B., et al. The polyphenolic-rich Aronia melanocarpa juice kills teratocarcinomal cancer stern-like cells, but not their differentiated counterparts. Journal of Functional Foods. 2013;5:1244–1252.
    1. Wang J., Lu M. L., Dai H. L., Zhang S. P., Wang H. X., Wei N. Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatoular carcinoma by initiating a mitochondrial-dependent apoptosis pathway. Brazilian Journal of Medical and Biological Research. 2015;48:245–253. doi: 10.1590/1414-431X20144074.
    1. Yang J., Xiao Y. L., He X. R., Qiu G. F., Hu X. M. Aesculetin-induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway in human cervical cancer cells. Journal of Asian Natural Products Research. 2010;12:185–193. doi: 10.1080/10286020903427336.
    1. Liang T., Zhang X., Xue W., Zhao S., Zhang X., Pei J. Curcumin induced human gastric cancer BGC-823 s apoptosis by ROS-mediated ASK1-MKK4-JNK stress signaling pathway. International Journal of Molecular Sciences. 2014;15:15754–15765. doi: 10.3390/ijms150915754.
    1. Lambert J. D., Elias R. J. The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Archives of Biochemistry and Biophysics. 2010;501:65–72. doi: 10.1016/j.abb.2010.06.013.
    1. Hwang J. T., Ha J., Park I. J., et al. Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway. Cancer Letters. 2007;247:115–121. doi: 10.1016/j.canlet.2006.03.030.
    1. Oikawa S., Furukawaa A., Asada H., Hirakawa K., Kawanishi S. Catechins induce oxidative damage to ular and isolated DNA through the generation of reactive oxygen species. Free Radical Research. 2003;37:881–890.
    1. Palit S., Kar S., Sharma G., Das P. K. Hesperetin induces apoptosis in breast carcinoma by triggering accumulation of ROS and activation of ASK1/JNK pathway. Journal of Cellular Physiology. 2015;230:1729–1739. doi: 10.1002/jcp.24818.
    1. Zhang Q., Cheng G., Qiu H., et al. The p53-inducible gene 3 involved in flavonoid-induced cytotoxicity through the reactive oxygen species-mediated mitochondrial apoptotic pathway in human hepatoma cells. Food & Function. 2015;6:1518–1525. doi: 10.1039/c5fo00142k.
    1. Kim G. T., Lee S. H., Kim Y. M. Quercetin regulates sestrin 2-AMPK-mTOR signaling pathway and induces apoptosis via increased intracellular ROS in HCT116 Colon cancer cells. Journal of Cancer Prevention. 2013;18:264–270.
    1. Iwasaki M., Inoue M., Otani T., et al. Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-based prospective study group. Journal of Clinical Oncology. 2008;26:1677–1683. doi: 10.1200/JCO.2007.13.9964.
    1. Jin S., Zhang Q. Y., Kang X. M., Wang J. X., Zhao W. H. Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway. Annals of Oncology. 2010;21:263–268. doi: 10.1093/annonc/mdp499.
    1. Lo Y.-L., Wang W., Ho C. T. 7,3′,4′-Trihydroxyisoflavone modulates multidrug resistance transporters and induces apoptosis via production of reactive oxygen species. Toxicology. 2012;302:221–232. doi: 10.1016/j.tox.2012.08.003.
    1. Yang X. J., Belosay A., Hartman J. A., et al. Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumors. Clinical & Experimental Metastasis. 2015;32:323–333. doi: 10.1007/s10585-015-9709-2.
    1. Rakshit S., Mandal L., Pal B. C., et al. Involvement of ROS in chlorogenic acid-induced apoptosis of Bcr-Abl+ CML cells. Biochemical Pharmacology. 2010;80:1662–1675. doi: 10.1016/j.bcp.2010.08.013.
    1. Kim K. K., Singh A. P., Singh R. K., et al. Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells. International Journal of Oncology. 2012;40:227–235. doi: 10.3892/ijo.2011.1198.
    1. Luo C., Li Y., Wang H., et al. Hydroxytyrosol promotes superoxide production and defects in autophagy leading to anti-proliferation and apoptosis on human prostate cancer cells. Current Cancer Drug Targets. 2013;13:625–639.
    1. Sun L. J., Luo C., Liu J. K. Hydroxytyrosol induces apoptosis in human colon cancer cells through ROS generation. Food & Function. 2014;5:1909–1914. doi: 10.1039/c4fo00187g.
    1. Guha P., Dey A., Sen R., Chatterjee M., Chattopadhyay S., Bandyopadhyay S. K. Intracellular GSH depletion triggered mitochondrial Bax translocation to accomplish resveratrol-induced apoptosis in the U937 cell line. The Journal of Pharmacology and Experimental Therapeutics. 2011;336:206–214. doi: 10.1124/jpet.110.171983.
    1. Alhosin M., Sharif T., Mousli M., et al. Down-regulation of UHRF1, associated with re-expression of tumor suppressor genes, is a common feature of natural compounds exhibiting anti-cancer properties. Journal of Experimental & Clinical Cancer Research. 2011;30 doi: 10.1186/1756-9966-30-41.
    1. Achour M., Mousli M., Alhosin M., et al. Epigallocatechin-3-gallate up-regulates tumor suppressor gene expression via a reactive oxygen species-dependent down-regulation of UHRF1. Biochemical and Biophysical Research Communications. 2013;430:208–212. doi: 10.1016/j.bbrc.2012.11.087.
    1. Kang J., Chen J., Shi Y., Jia J., Zhang Y. Curcumin-induced histone hypoacetylation: the role of reactive oxygen species. Biochemical Pharmacology. 2005;69:1205–1213. doi: 10.1016/j.bcp.2005.01.014.
    1. Rajendran P., Ho E., Williams D. E., Dashwood R. H. Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells. Clinical Epigenetics. 2011;3:p. 4. doi: 10.1186/1868-7083-3-4.
    1. Remely M., Lovrecic L., de la Garza A. L., et al. Therapeutic perspectives of epigenetically active nutrients. British Journal of Pharmacology. 2015;172:2756–2768. doi: 10.1111/bph.12854.
    1. Vanden Berghe W. Epigenetic impact of dietary polyphenols in chemoprevention: lifelong remodeling of our epigenomes. Pharmacological Research. 2012;65:565–576. doi: 10.1016/j.phrs.2012.03.007.
    1. Malireddy S., Kotha S. R., Secor J. D., et al. Phytochemical antioxidants modulate mammalian ular epigenome: implications in health and disease. Antioxidants & Redox Signaling. 2012;17:327–339. doi: 10.1089/ars.2012.4600.
    1. Ong T. P., Moreno F. S., Ross S. A. Targeting the epigenome with bioactive food components for cancer prevention. Journal of Nutrigenetics and Nutrigenomics. 2011;4:275–292. doi: 10.1159/000334585.
    1. Nakazato T., Ito K., Miyakawa Y., et al. Catechin, a green tea component, rapidly induces apoptosis of myeloid leukemic cells via modulation of reactive oxygen species production in vitro and inhibits tumor growth in vivo. Haematologica. 2005;90:317–325.
    1. Jeong J. C., Jang S. W., Kim T. H., Kwon C. H., Kim Y. K. Mulberry fruit (Moris fructus) extracts induce human glioma cell death in vitro through ROS-dependent mitochondrial pathway and inhibits glioma tumor growth in vivo. Nutrition and Cancer. 2010;62:402–412. doi: 10.1080/01635580903441287.
    1. Dent P., Yacoub A., Contessa J., et al. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiation Research. 2003;159(3):283–300.
    1. Mladenov E., Magin S., Soni A., Iliakis G. DNA double-strand-break repair in higher eukaryotes and its role in genomic instability and cancer: cell cycle and proliferation-dependent regulation. Seminars in Cancer Biology. 2016;37-38:51–64. doi: 10.1016/j.semcancer.2016.03.003.
    1. Roos W. P., Thomas A. D., Kaina B. DNA damage and the balance between survival and death in cancer biology. Nature Reviews Cancer. 2016;16(1):20–33. doi: 10.1038/nrc.2015.2.
    1. Ward J. F. DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability. Progress in Nucleic Acid Research and Molecular Biology. 1988;35:95–125.
    1. O’Driscoll M., Jeggo P. A. The role of double-strand break repair—insights from human genetics. Nature Reviews Genetics. 2006;7(1):45–54. doi: 10.1038/nrg1746.
    1. Jackson S. P., Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461(7267):1071–1078. doi: 10.1038/nature08467.
    1. Tubiana M. The role of local treatment in the cure of cancer. European Journal of Cancer. 1992;28A:2061–2069.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere