Oxidative Stress: Harms and Benefits for Human Health
This article is part of Special Issue:
Gabriele Pizzino,
Natasha Irrera,
Mariapaola Cucinotta,
Giovanni Pallio,
Federica Mannino,
Vincenzo Arcoraci,
Francesco Squadrito,
Domenica Altavilla,
Alessandra Bitto,
Corresponding Author
Gabriele Pizzino
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorNatasha Irrera
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorMariapaola Cucinotta
Department of Biomedical Sciences, Dentistry and Morphological and Functional Images, University of Messina, Messina, Italy unime.it
Search for more papers by this authorGiovanni Pallio
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorFederica Mannino
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorVincenzo Arcoraci
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorFrancesco Squadrito
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorDomenica Altavilla
Department of Biomedical Sciences, Dentistry and Morphological and Functional Images, University of Messina, Messina, Italy unime.it
Search for more papers by this authorAlessandra Bitto
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorGabriele Pizzino,
Natasha Irrera,
Mariapaola Cucinotta,
Giovanni Pallio,
Federica Mannino,
Vincenzo Arcoraci,
Francesco Squadrito,
Domenica Altavilla,
Alessandra Bitto,
Corresponding Author
Gabriele Pizzino
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorNatasha Irrera
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorMariapaola Cucinotta
Department of Biomedical Sciences, Dentistry and Morphological and Functional Images, University of Messina, Messina, Italy unime.it
Search for more papers by this authorGiovanni Pallio
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorFederica Mannino
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorVincenzo Arcoraci
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorFrancesco Squadrito
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorDomenica Altavilla
Department of Biomedical Sciences, Dentistry and Morphological and Functional Images, University of Messina, Messina, Italy unime.it
Search for more papers by this authorAlessandra Bitto
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy unime.it
Search for more papers by this authorAcademic Editor: Victor M. Victor
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., and Ebine T., Differential cellular localization of antioxidant enzymes in the trigeminal ganglion, Neuroscience. (2013) 248, 345–358, 23774632, https://doi.org/10.1016/j.neuroscience.2013.06.010, 2-s2.0-84880613255.
- 2 Navarro-Yepes J., Zavala-Flores L., Anandhan A., Wang F., Skotak M., and Chandra N., Antioxidant gene therapy against neuronal cell death, Pharmacology & Therapeutics. (2014) 142, 206–230, 24333264, https://doi.org/10.1016/j.pharmthera.2013.12.007, 2-s2.0-84896399040.
- 3 Rajendran P., Nandakumar N., Rengarajan T., Palaniswami R., Gnanadhas E. N., and Lakshminarasaiah U., Antioxidants and human diseases, Clinica Chimica Acta. (2014) 436, 332–347, 24933428, https://doi.org/10.1016/j.cca.2014.06.004, 2-s2.0-84904052451.
- 4 Wu J. Q., Kosten T. R., and Zhang X. Y., Free radicals, antioxidant defense system, and schizophrenia, Progress in Neuro-Psychopharmacology & Biological Psychiatry. (2013) 46, 200–206, 23470289, https://doi.org/10.1016/j.pnpbp.2013.02.015, 2-s2.0-84883551131.
- 5 Taniyama Y. and Griendling K. K., Reactive oxygen species in the vasculature, Hypertension. (2003) 42, 1075–1081, 14581295, https://doi.org/10.1161/01.HYP.0000100443.09293.4F, 2-s2.0-0348109425.
- 6 Al-Gubory K. H., Garrel C., Faure P., and Sugino N., Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress, Reproductive Biomedicine Online. (2012) 25, 551–560, 23063822, https://doi.org/10.1016/j.rbmo.2012.08.004, 2-s2.0-84870519819.
- 7 Hansen J. M., Go Y. M., and Jones D. P., Nuclear and mitochondrial compartmentation of oxidative stress and redox signalling, Annual Review of Pharmacology and Toxicology. (2006) 46, 215–234, 16402904, https://doi.org/10.1146/annurev.pharmtox.46.120604.141122, 2-s2.0-33144490305.
- 8 Glasauer A. and Chandel N. S., Targeting antioxidants for cancer therapy, Biochemical Pharmacology. (2014) 92, 90–101, 25078786, https://doi.org/10.1016/j.bcp.2014.07.017, 2-s2.0-84908153270.
- 9 Deponte M., Glutathione catalysis and the reaction mechanism of glutathione-dependent enzymes, Biochimica et Biophysica Acta. (1830) 2013, 3217–3266, 23036594, https://doi.org/10.1016/j.bbagen.2012.09.018, 2-s2.0-84875737737.
- 10 Halliwell B. and Gutteridge J. M. C., Free Radicals in Biology and Medicine, 2007, 4th edition, Clarendon Press, Oxford, UK.
- 11 Bahorun T., Soobrattee M. A., Luximon-Ramma V., and Aruoma O. I., Free radicals and antioxidants in cardiovascular health and disease, Internet Journal of Medical Update. (2006) 1, 1–17.
- 12
Kumar S. and
Pandey A. K., Free radicals: health implications and their mitigation by herbals, British Journal of Medicine and Medical Research. (2015) 7, 438–457.
10.9734/BJMMR/2015/16284 Google Scholar
- 13 Kumar S. and Pandey A. K., Chemistry and biological activities of flavonoids: an overview, The Scientific World Journal. (2013) 2013, 16, 162750, 24470791, https://doi.org/10.1155/2013/162750, 2-s2.0-84896281851.
- 14 Valko M., Izakovic M., Mazur M., Rhodes C. J., and Telser J., Role of oxygen radicals in DNA damage and cancer incidence, Molecular and Cellular Biochemistry. (2004) 266, 37–56, 15646026.
- 15 Valko M., Leibfritz D., Moncola J., Cronin M. D., Mazur M., and Telser J., Free radicals and antioxidants in normal physiological functions and human disease, The International Journal of Biochemistry & Cell Biology. (2007) 39, 44–84, 16978905, https://doi.org/10.1016/j.biocel.2006.07.001, 2-s2.0-33749986298.
- 16 Droge W., Free radicals in the physiological control of cell function, Physiological Reviews. (2002) 82, 47–95, 11773609, https://doi.org/10.1152/physrev.00018.2001.
- 17 Willcox J. K., Ash S. L., and Catignani G. L., Antioxidants and prevention of chronic disease, Critical Reviews in Food Science and Nutrition. (2004) 44, 275–295, 15462130, https://doi.org/10.1080/10408690490468489, 2-s2.0-4644318696.
- 18 Pacher P., Beckman J. S., and Liaudet L., Nitric oxide and peroxynitrite in health and disease, Physiological Reviews. (2007) 87, 315–424, 17237348, https://doi.org/10.1152/physrev.00029.2006, 2-s2.0-33846863589.
- 19 Genestra M., Oxyl radicals, redox-sensitive signalling cascades and antioxidants, Cellular Signalling. (2007) 19, 1807–1819, 17570640, https://doi.org/10.1016/j.cellsig.2007.04.009, 2-s2.0-34447631168.
- 20 Halliwell B., Biochemistry of oxidative stress, Biochemical Society Transactions. (2007) 35, 1147–1150, 17956298, https://doi.org/10.1042/BST0351147, 2-s2.0-36749010860.
- 21 Young I. and Woodside J., Antioxidants in health and disease, Journal of Clinical Pathology. (2001) 54, 176–186, 11253127.
- 22 Valko M., Rhodes C. J., Moncol J., Izakovic M., and Mazur M., Free radicals, metals and antioxidants in oxidative stress-induced cancer, Chemico-Biological Interactions. (2006) 160, 1–40, 16430879, https://doi.org/10.1016/j.cbi.2005.12.009, 2-s2.0-32444433202.
- 23 Valko M., Morris H., and Cronin M. T. D., Metals, toxicity and oxidative stress, Current Medicinal Chemistry. (2005) 12, 1161–1208, 15892631.
- 24 Parthasarathy S., Santanam N., Ramachandran S., and Meilhac O., Oxidants and antioxidants in atherogenesis: an appraisal, Journal of Lipid Research. (1999) 40, 2143–2157, 10588940.
- 25 Frei B., Reactive Oxygen Species and Antioxidant Vitamins, 1997, Linus Pauling Institute, Oregon State University, http://lpi.oregonstate.edu/f-w97/reactive.html.
- 26 Nishida N., Arizumi T., Takita M., Kitai S., Yada N., Hagiwara S., Inoue T., Minami Y., Ueshima K., Sakurai T., and Kudo M., Reactive oxygen species induce epigenetic instability through the formation of 8-hydroxydeoxyguanosine in human hepatocarcinogenesis, Digestive Diseases. (2013) 31, no. 5-6, 459–466, 24281021, https://doi.org/10.1159/000355245, 2-s2.0-84890035596.
- 27 Yasui M., Kanemaru Y., Kamoshita N., Suzuki T., Arakawa T., and Honma M., Tracing the fates of site-specifically introduced DNA adducts in the human genome, DNA Repair (Amst). (2014) 15, 11–20, 24559511, https://doi.org/10.1016/j.dnarep.2014.01.003, 2-s2.0-84893721705.
- 28 Valavanidis A., Vlachogianni T., Fiotakis K., and 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, no. 9, 3886–3907, 23985773, https://doi.org/10.3390/ijerph10093886, 2-s2.0-84883405516.
- 29 Pizzino G., Bitto A., Interdonato M., Galfo F., Irrera N., Mecchio A., Pallio G., Ramistella V., LucaF.De, Minutoli L., Squadrito F., and Altavilla D., 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, 24936443, https://doi.org/10.1016/j.redox.2014.05.003, 2-s2.0-84901388600.
- 30 Chatterjee M., Saluja R., Kanneganti S., Chinta S., and Dikshit M., Biochemical and molecular evaluation of neutrophil NOS in spontaneously hypertensive rats, Cellular and Molecular Biology. (2007) 53, 84–93, 17519116.
- 31 Ceriello A., Possible role of oxidative stress in the pathogenesis of hypertension, Diabetes Care. (2008) 31, no. Supplement 2, S181–S184, 18227482, https://doi.org/10.2337/dc08-s245.
- 32 Halliwell B., Role of free radicals in neurodegenerative diseases: therapeutic implications for antioxidant treatment, Drugs & Aging. (2001) 18, 685–716, 11599635.
- 33 Singh R. P., Sharad S., and Kapur S., Free radicals and oxidative stress in neurodegenerative diseases: relevance of dietary antioxidants, Journal, Indian Academy of Clinical Medicine. (2004) 5, 218–225.
- 34 Christen Y., Oxidative stress and Alzheimer disease, The American Journal of Clinical Nutrition. (2000) 71, 621S–629S, 10681270.
- 35 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, 12607822.
- 36 Caramori G. and Papi A., Oxidants and asthma, Thorax. (2004) 59, 170–173, 14760161.
- 37 Guo R. F. and Ward P. A., Role of oxidants in lung injury during sepsis, Antioxidants & Redox Signaling. (2007) 9, 1991–2002, 17760509, https://doi.org/10.1089/ars.2007.1785, 2-s2.0-35448941488.
- 38 Hoshino Y. and Mishima M., Antioxidants & redox signaling redox-based therapeutics for lung diseases, Antioxidants & Redox Signaling. (2008) 10, 701–704, 18177233, https://doi.org/10.1089/ars.2007.1961, 2-s2.0-38949085943.
- 39 MacNee W., Oxidative stress and lung inflammation in airways disease, European Journal of Pharmacology. (2001) 429, 195–207, 11698041.
- 40 Walston J., Xue Q., Semba R. D., Ferrucci L., Cappola A. R., Ricks M., Guralnik J., and Fried L. P., Serum antioxidants, inflammation, and total mortality in older women, American Journal of Epidemiology. (2006) 163, 18–26, 16306311, https://doi.org/10.1093/aje/kwj007, 2-s2.0-29344469588.
- 41 Mahajan A. and Tandon V. R., Antioxidants and rheumatoid arthritis, Journal of Indian Rheumatology Association. (2004) 12, 139–142.
- 42 Galle J., Oxidative stress in chronic renal failure, Nephrology, Dialysis, Transplantation. (2001) 16, 2135–2142.
- 43 Sadeg N., Pham-Huy C., Martin C., Warnet J. M., and 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, 8486097, https://doi.org/10.3109/01480549309031994, 2-s2.0-0027529297.
- 44 Massicot F., Martin C., Dutertre-Catella H., Ellouk-Achard S., Pham-Huy C., Thevenin M., Rucay P., Warnet J. M., and Claude J. R., 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, 9248632.
- 45 Massicot F., Lamouri A., Martin C., Pham-Huy C., Heymans F., Warnet J. M., Godfroid J. J., and Claude J. R., 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, 9034965.
- 46 Samuel J. B., Stanley J. A., Princess R. A., Shanthi P., and Sebastian M. S., Gestational cadmium exposure-induced ovotoxicity delays puberty through oxidative stress and impaired steroid hormone levels, Journal of Medical Toxicology. (2011) 7, no. 3, 195–204, 21373971, https://doi.org/10.1007/s13181-011-0143-9, 2-s2.0-79961171902.
- 47 Interdonato M., Pizzino G., Bitto A., Galfo F., Irrera N., Mecchio A., Pallio G., Ramistella V., LucaF.De, Santamaria A., Minutoli L., Marini H., Squadrito F., and Altavilla D., Cadmium delays puberty onset and testis growth in adolescents, Clinical Endocrinology. (2015) 83, no. 3, 357–362, 25521350, https://doi.org/10.1111/cen.12704, 2-s2.0-84940448175.
- 48 Mene-Saffrane L. and DellaPenna D., Biosynthesis, regulation and functions of tocochromanols in plants, Plant Physiology and Biochemistry. (2010) 48, 301–309, 20036132, https://doi.org/10.1016/j.plaphy.2009.11.004, 2-s2.0-77953137753.
- 49 Sheppard A., Pennington J. A. T., and Weihrauch J. L., F. J. Packer, Analysis and distribution of vitamin E in vegetable oils and foods, Vitamin E in Health and Disease, 1993, Marcel Dekker Inc, New York, 9–31.
- 50 Sundl I., Murkovic M., Bandoniene D., and 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, 17055122, https://doi.org/10.1016/j.clnu.2006.06.003, 2-s2.0-33846575622.
- 51 Boscoboinik D., Szewczyk A., Hensey C., and Azzi A., Inhibition of cell proliferation by alpha-tocopherol. Role of protein kinase C, The Journal of Biological Chemistry. (1991) 266, 6188–6194, 2007576.
- 52 Özer N. K., Palozza P., Boscoboinik D., and 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, 8486164.
- 53 Sirikci Ö., Özer N. K., and 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, 8902151.
- 54 Özer N. K., Sirikci O., Taha S., San T., Moser U., and Azzi A., Effect of vitamin E and probucol on dietary cholesterol-induced atherosclerosis in rabbits, Free Radical Biology & Medicine. (1998) 24, 226–233, 9433896.
- 55 Meydani M., Kwan P., Band M., Knight A., Guo W., Goutis J., and Ordovas J., Long-term vitamin E supplementation reduces atherosclerosis and mortality in Ldlr−/− mice, but not when fed Western style diet, Atherosclerosis. (2014) 233, 196–205, 24529144, https://doi.org/10.1016/j.atherosclerosis.2013.12.006, 2-s2.0-84893822158.
- 56 KeaneyJ. F.Jr., Simon D. I., and Freedman J. E., Vitamin E and vascular homeostasis: implications for atherosclerosis, The FASEB Journal. (1999) 13, 965–975, 10336880.
- 57 Febbraio M., Podrez E., Smith J., Hajjar D., Hazen S., Hoff H., Sharma K., and Silverstein R., Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice, Journal of Clinical Investigation. (2000) 105, 1049–1056, 10772649, https://doi.org/10.1172/JCI9259.
- 58 Ozer N. K., Negis Y., Aytan N., Villacorta L., Ricciarelli R., Zingg J. M., and Azzi A., Vitamin E inhibits CD36 scavenger receptor expression in hypercholesterolemic rabbits, Atherosclerosis. (2006) 184, 15–20, 15979077, https://doi.org/10.1016/j.atherosclerosis.2005.03.050, 2-s2.0-28344442724.
- 59 Ricciarelli R., Zingg J. M., and 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, 10880419.
- 60 Tang F., Lu M., Zhang S., Mei M., Wang T., Liu P., and Wang H., Vitamin E conditionally inhibits atherosclerosis in ApoE knockout mice by anti-oxidation and regulation of vasculature gene expressions, Lipids. (2014) 49, 1215–1223, 25385496, https://doi.org/10.1007/s11745-014-3962-z, 2-s2.0-84922073945.
- 61 Catalgol B., Ziaja I., Breusing N., Jung T., Hohn A., Alpertunga B., Schroeder P., Chondrogianni N., Gonos E. S., Petropoulos I., Friguet B., Klotz L. O., Krutmann J., and Grune T., The proteasome is an integral part of solar ultraviolet a radiation-induced gene expression, The Journal of Biological Chemistry. (2009) 284, 30076–30086, 19690165, https://doi.org/10.1074/jbc.M109.044503, 2-s2.0-71049176929.
- 62 Hershko A. and Ciechanover A., The ubiquitin system, Annual Review of Biochemistry. (1998) 67, 425–479, 9759494, https://doi.org/10.1146/annurev.biochem.67.1.425, 2-s2.0-0031657807.
- 63 Sozen E., Karademir B., Yazgan B., Bozaykut P., and Ozer N. K., Potential role of proteasome on c-Jun related signaling in hypercholesterolemia induced atherosclerosis, Redox Biology. (2014) 2, 732–738, 25009774, https://doi.org/10.1016/j.redox.2014.02.007, 2-s2.0-84904671097.
- 64 Otero P., Bonet B., Herrera E., and Rabano A., Development of atherosclerosis in the diabetic BALB/c mice. Prevention with vitamin E administration, Atherosclerosis. (2005) 182, 259–265, 16159598, https://doi.org/10.1016/j.atherosclerosis.2005.02.024, 2-s2.0-24644498663.
- 65 Huang Z. G., Liang C., Han S. F., and 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, 22139346, https://doi.org/10.1007/s11010-011-1153-2, 2-s2.0-84857906598.
- 66 Gaedicke S., Zhang X., Schmelzer C., Lou Y., Doering F., Frank J., and Rimbach G., Vitamin E dependent microRNA regulation in rat liver, FEBS Letters. (2008) 582, 3542–3546, 18817776, https://doi.org/10.1016/j.febslet.2008.09.032, 2-s2.0-53049092870.
- 67 Barella L., Muller P. Y., Schlachter M., Hunziker W., Stocklin E., Spitzer V., Meier N., de Pascual-Teresa S., Minihane A. M., and Rimbach G., 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, 15158915, https://doi.org/10.1016/j.bbadis.2004.02.002, 2-s2.0-2442641218.
- 68 Podszun M. C., Grebenstein N., Spruss A., Schlueter T., Kremoser C., Bergheim I., and Frank J., 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, 24725433, https://doi.org/10.1016/j.jnutbio.2014.01.008, 2-s2.0-84897950596.
- 69 Abdala-Valencia H., Berdnikovs S., Soveg F., and 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, 25015974, https://doi.org/10.1152/ajplung.00132.2014, 2-s2.0-84908513572.
- 70 Abdala-Valencia H., Soveg F., and 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, 26801566, https://doi.org/10.1152/ajplung.00301.2015, 2-s2.0-84984650503.
- 71 Cook-Mills J. M. and Avila P. C., Vitamin E and D regulation of allergic asthma immunopathogenesis, International Immunopharmacology. (2014) 23, 364–372, 25175918, https://doi.org/10.1016/j.intimp.2014.08.007, 2-s2.0-84910644095.
- 72 Marchese M. E., Kumar R., Colangelo L. A., Avila P. C., JacobsD. R.Jr., Gross M., Sood A., Liu K., and Cook-Mills J. M., The vitamin E isoforms alpha-tocopherol and gamma-tocopherol have opposite associations with spirometric parameters: the CARDIA study, Respiratory Research. (2014) 15, 24629024, https://doi.org/10.1186/1465-9921-15-31, 2-s2.0-84899066579.
- 73 Cook-Mills J. M., Isoforms of vitamin E differentially regulate PKC alpha and inflammation: a review, Journal of Clinical & Cellular Immunology. (2013) 4, no. 137, 23977443, https://doi.org/10.4172/2155-9899.1000137.
- 74 Cook-Mills J. M., Abdala-Valencia H., and Hartert T., Two faces of vitamin e in the lung, American Journal of Respiratory and Critical Care Medicine. (2013) 188, 279–284, 23905522, https://doi.org/10.1164/rccm.201303-0503ED, 2-s2.0-84881158525.
- 75 Abdala-Valencia H., Berdnikovs S., and 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, 22815910, https://doi.org/10.1371/journal.pone.0041054, 2-s2.0-84864006003.
- 76 McCary C. A., Abdala-Valencia H., Berdnikovs S., and 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, 21317387, https://doi.org/10.4049/jimmunol.1003037, 2-s2.0-79953219059.
- 77 Cook-Mills J. M. and McCary C. A., Isoforms of vitamin E differentially regulate inflammation, Endocrine, Metabolic & Immune Disorders Drug Targets. (2010) 10, 348–366, 20923401.
- 78 Cook-Mills J. M., Marchese M. E., and 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, 21050132, https://doi.org/10.1089/ars.2010.3522, 2-s2.0-79961181296.
- 79 Abdala-Valencia H. and Cook-Mills J. M., VCAM-1 signals activate endothelial cell protein kinase Cα via oxidation, Journal of Immunology. (2006) 177, 6379–6387, 17056569.
- 80 Berdnikovs S., Abdala-Valencia H., McCary C., Somand M., Cole R., Garcia A., Bryce P., and Cook-Mills J., Isoforms of vitamin E have opposing immunoregulatory funcitons during inflammation by regulating leukocyte recruitment, Journal of Immunology. (2009) 182, 4395–4405, 19299740, https://doi.org/10.4049/jimmunol.0803659, 2-s2.0-64249131071.
- 81 Cook-Mills J. M., Gebretsadik T., Abdala-Valencia H., Green J., Larkin E. K., Dupont W. D., Shu X. O., Gross M., Bai C., Gao Y., Hartman T. J., Rosas-Salazar C., and Hartert T., Brief research report: interaction of vitamin E isoforms on asthma and allergic airway disease, Thorax. (2016) 71, 954–956, 27257004, https://doi.org/10.1136/thoraxjnl-2016-208494, 2-s2.0-84973320500.
- 82 Wu D., Han S. N., Meydani M., and 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, 16943451.
- 83 Christiani D. C., Ye T. T., Wegman D. H., Eisen E. A., Dai H. L., and 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, 8205865.
- 84 Jacobs R. R., Boehlecke B., van Hage-Hamsten M., and Rylander R., Bronchial reactivity, atopy, and airway response to cotton dust, The American Review of Respiratory Disease. (1993) 148, 19–24, 8317797, https://doi.org/10.1164/ajrccm/148.1.19.
- 85 Delfino R. J., Quintana P. J., Floro J., Gastanaga V. M., Samimi B. S., Kleinman M. T., Liu L. J., Bufalino C., Wu C. F., and McLaren C. E., Association of FEV1 in asthmatic children with personal and microenvironmental exposure to airborne particulate matter, Environmental Health Perspectives. (2004) 112, 932–941, 15175185.
- 86 Koskela H., Tukiainen H., Kononoff A., and Pekkarinen H., Effect of whole-body exposure to cold and wind on lung function in asthmatic patients, Chest. (1994) 105, 1728–1731, 8205867.
- 87 Blanc P. D., Eisner M. D., Katz P. P., Yen I. H., Archea C., Earnest G., Janson S., Masharani U. B., Quinlan P. J., Hammond S. K., Thorne P. S., Balmes J. R., Trupin L., and Yelin E. H., Impact of the home indoor environment on adult asthma and rhinitis, Journal of Occupational and Environmental Medicine. (2005) 47, 362–372, 15824627.
- 88 Fedulov A. V. and 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, 20118218, https://doi.org/10.1165/rcmb.2009-0400OC, 2-s2.0-79952211475.
- 89 Lim R. H. and Kobzik L., Maternal transmission of asthma risk, American Journal of Reproductive Immunology. (2009) 61, 1–10, 19007349, https://doi.org/10.1111/j.1600-0897.2008.00671.x, 2-s2.0-57749208485.
- 90 Langlet C., Springael C., Johnson J., Thomas S., Flamand V., Leitges M., Goldman M., Aksoy E., and Willems F., 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, 19950169, https://doi.org/10.1002/eji.200939391, 2-s2.0-75149162956.
- 91 Cejas P. J., Carlson L. M., Zhang J., Padmanabhan S., Kolonias D., Lindner I., Haley S., Boise L. H., and Lee K. P., 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, 15917249, https://doi.org/10.1074/jbc.M500345200, 2-s2.0-23344448482.
- 92 Lin Y. F., Lee H. M., Leu S. J., and 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, 17455194, https://doi.org/10.1002/jcb.21305, 2-s2.0-34948840876.
- 93 Lin Y. F., Leu S. J., Huang H. M., and 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, 20626007, https://doi.org/10.1002/jcp.22312, 2-s2.0-78049255849.
- 94 Asehnoune K., Strassheim D., Mitra S., Yeol Kim J., and Abraham E., Involvement of PKCalpha/beta in TLR4 and TLR2 dependent activation of NF-kappaB, Cellular Signalling. (2005) 17, 385–394, 15567069, https://doi.org/10.1016/j.cellsig.2004.08.005, 2-s2.0-9644264080.
- 95 Ramadan G., Schmidt R. E., and 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, 11529915.
- 96 Davis T. A., Saini A. A., Blair P. J., Levine B. L., Craighead N., Harlan D. M., June C. H., and Lee K. P., 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, 9558069.
- 97 Rajotte D., Haddad P., Haman A., CragoeE. J.Jr., and 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, 1315776.
- 98 Salh B., Hoeflick K., Kwan W., and 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, 9824513.
- 99 St Louis D. C., Woodcock J. B., Franzoso G., Blair P. J., Carlson L. M., Murillo M., Wells M. R., Williams A. J., Smoot D. S., Kaushal S., Grimes J. L., Harlan D. M., Chute J. P., June C. H., Siebenlist U., and Lee K. P., 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, 10092775.
- 100 Cejas P. J., Carlson L. M., Kolonias D., Zhang J., Lindner I., Billadeau D. D., Boise L. H., and Lee K. P., Regulation of RelB expression during the initiation of dendritic cell differentiation, Molecular and Cellular Biology. (2005) 25, 7900–7916, 16107733, https://doi.org/10.1128/MCB.25.17.7900-7916.2005, 2-s2.0-23844451425.
- 101 Farren M. R., Carlson L. M., and 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, 19756409, https://doi.org/10.1007/s12026-009-8118-5, 2-s2.0-77949390562.
- 102 Geijsen N., Spaargaren M., Raaijmakers J. A., Lammers J. W., Koenderman L., and 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, 10490850, https://doi.org/10.1038/sj.onc.1202896, 2-s2.0-0033538977.
- 103 Verdelli D., Nobili L., Todoerti K., Intini D., Cosenza M., Civallero M., Bertacchini J., Deliliers G. L., Sacchi S., Lombardi L., and Neri A., 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, 18759374, https://doi.org/10.1002/hon.875, 2-s2.0-65249135021.
- 104 Hamdorf M., Berger A., Schule S., Reinhardt J., and Flory E., PKCdelta-induced PU.1 phosphorylation promotes hematopoietic stem cell differentiation to dendritic cells, Stem Cells. (2011) 29, 297–306, 21732487, https://doi.org/10.1002/stem.564, 2-s2.0-79952140773.
- 105 Lee J. S., Kim I. S., Ryu J. S., and 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, 18490175, https://doi.org/10.1016/j.cyto.2008.03.010, 2-s2.0-44449177776.
- 106 Guler R., Afshar M., Arendse B., Parihar S. P., Revaz-Breton M., Leitges M., Schwegmann A., and Brombacher F., 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, 21287553, https://doi.org/10.1002/eji.201040985, 2-s2.0-79951775594.
- 107 McCary C. A., Yoon Y., Panagabko C., Cho W., Atkinson J., and Cook-Mills J. M., Vitamin E isoforms directly bind PKCalpha and differentially regulate activation of PKCalpha, The Biochemical Journal. (2012) 441, 189–198, 21933153, https://doi.org/10.1042/BJ20111318, 2-s2.0-84055223637.
- 108 Mahomoodally M. F., Gurib-Fakim A., and Subratty A. H., Antimicrobial activities and phytochemical profiles of endemic medicinal plants of Mauritius, Pharmaceutical Biology. (2005) 43, no. 3, 237–242.
- 109 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, no. 11-12, 383–386.
- 110 Heim K. E., Tagliaferro A. R., and Bobilya D. J., Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships, Journal of Nutritional Biochemistry. (2002) 13, no. 10, 572–584, 12550068.
- 111 Kumar S., Mishra A., and 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, 23721571, https://doi.org/10.1186/1472-6882-13-120, 2-s2.0-84878254009.
- 112
Kumar S. and
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, https://doi.org/10.5958/j.2229-4473.26.1.043, 2-s2.0-84880370306.
10.5958/j.2229-4473.26.1.043 Google Scholar
- 113 Leopoldini M., Russo N., Chiodo S., and Toscano M., Iron chelation by the powerful antioxidant flavonoid quercetin, Journal of Agricultural and Food Chemistry. (2006) 54, no. 17, 6343–6351, 16910729, https://doi.org/10.1021/jf060986h, 2-s2.0-84961979266.
- 114 Kumar S., Gupta A., and Pandey A. K., Calotropis procera root extract has capability to combat free radical mediated damage, ISRN Pharmacology. (2013) 2013, 8, 691372, 24222863, https://doi.org/10.1155/2013/691372.
- 115 Cook N. C. and Samman S., Review: flavonoids-chemistry, metabolism, cardioprotective effects and dietary sources, Journal of Nutritional Biochemistry. (1996) 7, no. 2, 66–76.
- 116 Rice-Evans C. A., Miller N. J., Bolwell P. G., Broamley P. M., and Pridham J. B., The relative antioxidant activities of plant-derived polyphenolic flavonoids, Free Radical Research. (1995) 22, no. 4, 375–383, 7633567.
- 117 Pandey A. K., Mishra A. K., and 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, 23273204.
- 118 Halliwell B. and Gutteridge J. M. C., Free Radicals in Biology and Medicine, 1998, Oxford University Press, Oxford, UK.
- 119 Mishra A., Kumar S., and Pandey A. K., Scientific validation of the medicinal efficacy of Tinospora cordifolia, The Scientific World Journal. (2013) 2013, 8, 292934, 24453828, https://doi.org/10.1155/2013/292934, 2-s2.0-84896308673.
- 120 Ganai A. A., Khan A. A., Malik Z. A., and 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, 25620059, https://doi.org/10.1016/j.taap.2015.01.012, 2-s2.0-84921860740.
- 121 Clarkson T. B., Anthony M. S., and 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, 11231976, https://doi.org/10.1210/jcem.86.1.7151.
- 122 Adams M. R., Golden D. L., Williams J. K., Franke A. A., Register T. C., and 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, 16317131.
- 123 Yamakoshi J., Piskula M. K., Izumi T., Tobe K., Saito M., Kataoka S., Obata A., and Kikuchi M., Isoflavone aglycone-rich extract without soy protein attenuates atherosclerosis development in cholesterol-fed rabbits, The Journal of Nutrition. (2000) 130, 1887–1893, 10917898.
- 124 Kanazawa T., Osanai T., Zhang X. S., Uemura T., Yin X. Z., Onodera K., Oike Y., and Ohkubo K., Protective effects of soy protein on the peroxidizability of lipoproteins in cerebrovascular diseases, The Journal of Nutrition. (1995) 125, 639S–646S, 7884546.
- 125 Tikkanen M. J., Wahala K., Ojala S., Vihma V., and 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, 9501223.
- 126 Wiseman H., O’Reilly J. D., Adlercreutz H., Mallet A. I., Bowey E. A., Rowland I. R., and Sanders T. A., 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, 10919933.
- 127 Ryan-Borchers T. A., Park J. S., Chew B. P., McGuire M. K., Fournier L. R., and Beerman K. A., Soy isoflavones modulate immune function in healthy postmenopausal women, The American Journal of Clinical Nutrition. (2006) 83, 1118–1125, 16685055.
- 128 Hodgson J. M., Puddey I. B., Croft K. D., Mori T. A., Rivera J., and Beilin L. J., Isoflavonoids do not inhibit in vivo lipid peroxidation in subjects with high-normal blood pressure, Atherosclerosis. (1999) 145, 167–172, 10428307.
- 129 Samman S., Lyons Wall P. M., Chan G. S., Smith S. J., and 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, 10559513.
- 130 Vega-Lopez S., Yeum K. J., Lecker J. L., Ausman L. M., Johnson E. J., Devaraj S., Jialal I., and Lichtenstein A. H., 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, 15640458.
- 131 Choi C., Cho H., Park J., Cho C., and 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, 14519976, https://doi.org/10.1271/bbb.67.1916, 2-s2.0-2842570563.
- 132 Naidu K. A., Vitamin C in human health and disease is still a mystery? An overview, Nutrition Journal. (2003) 2, 14498993, https://doi.org/10.1186/1475-2891-2-7, 2-s2.0-3042559581.
- 133 Crott J. W. and Fenech M., Effect of vitamin C supplementation on chromosome damage, apoptosis and necrosis ex vivo, Carcinogenesis. (1999) 20, no. 6, 1035–1041, 10357785.
- 134 Carr A. C. and Frei B., Does vitamin C act as pro-oxidant under physiological conditions?, FASEB Journal. (1999) 13, 1007–1024, 10336883.
- 135 Suzuki K., Koike H., Matsui H., Ono Y., Hasumi M., Nakazato H., Okugi H., Sekine Y., Oki K., Ito K., Yamamoto T., Fukabori Y., Kurokawa K., and Yamanaka H., 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, 12115487, https://doi.org/10.1002/ijc.10428, 2-s2.0-0037142176.
- 136 Raschke M., Rowland I. R., Magee P. J., and 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, 16774941, https://doi.org/10.1093/carcin/bgl082, 2-s2.0-33750437435.
- 137 Takada Y., Mukhopadhyay A., Kundu G. C., Mahabeleshwar G. H., Singh S., and 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, no. 26, 24233–24241, 12711606, https://doi.org/10.1074/jbc.M212389200, 2-s2.0-0037591401.
- 138 Harakeh S., Diab-Assaf M., Khalife J. C., Abu-el-Ardat K. A., Baydoun E., Niedzwiecki A., El-Sabban M. E., and Rath M., Ascorbic acid induces apoptosis in adult T-cell leukemia, Anticancer Research. (2007) 27, no. 1A, 289–298, 17352246.
- 139 Nakano H., Nakajima A., Sakon-Komazawa S., Piao J. H., Xue X., and Okumura K., Reactive oxygen species mediate crosstalk between NF-kappaB and JNK, Cell Death and Differentiation. (2006) 13, no. 5, 730–777, 16341124, https://doi.org/10.1038/sj.cdd.4401830, 2-s2.0-33645965616.
- 140 Belin S., Kaya F., Duisit G., Giacometti S., Ciccolini J., and Fontés M., Antiproliferative effect of ascorbic acid is associated with the inhibition of genes necessary to cell cycle progression, PLoS One. (2009) 4, no. 2, 19197388, https://doi.org/10.1371/journal.pone.0004409, 2-s2.0-84860475014.
- 141 Migliozzi J. A., Effect of ascorbic acid on tumour growth, British Journal of Cancer. (1977) 35, 869983.
- 142 Kishino K., Hashimoto K., Amano O., Kochi M., Liu W., and Sakagami H., Tumor-specific cytotoxicity and type of cell death induced by sodium 5,6-benzylidene-l-ascorbate, Anticancer Research. (2008) 28, 2577–2584, 19035281.
- 143 Chen Q., Espey M. G., Sun A. Y., Pooput C., Kirk K. L., Krishna M. C., Khosh D. B., Drisko J., and Levine M., 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, no. 32, 11105–11109, 18678913, https://doi.org/10.1073/pnas.0804226105, 2-s2.0-49649115940.
- 144 Chen Q., Espey M. G., Sun A. Y., Lee J.-H., Krishna M. C., Shacter E., Choyke P. L., Pooput C., Kirk K. L., Buettner G. R., and Levine M., 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, no. 21, 8749–8754, 17502596, https://doi.org/10.1073/pnas.0702854104, 2-s2.0-34547429599.
- 145 Richardson D. R. and Ponka P., The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells, Biochimica et Biophysica Acta. (1997) 1331, no. 1, 1–40, 9325434.
- 146 Hann H. W., Evans A. E., Siegel S. E., Wong K. Y., Sather H., Dalton A., Hammond D., and Seeger R. C., Prognostic importance of serum ferritin in patients with stages III and IV neuroblastoma: the Children’s Cancer Study Group experience, Cancer Research. (1985) 45, no. 6, 2843–2848, 3986811.
- 147 Shen L., Zhao H. Y., Du J., and Wang F., Anti-tumor activities of four chelating agents against human neuroblastoma cells, In Vivo. (2005) 19, no. 1, 233–236, 15796180.
- 148 Chen Q., Espey M. G., Krishna M. C., Mitchell J. B., Corpe C. P., Buettner G. R., Shacter E., and Levine M., 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, no. 38, 13604–13609, 16157892, https://doi.org/10.1073/pnas.0506390102, 2-s2.0-26444521256.
- 149 Bhat S. H., Azmi A. S., Hanif S., and 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, 16861029, https://doi.org/10.1016/j.biocel.2006.05.017, 2-s2.0-33748766854.
- 150 Kinoshita N., Yamamura T., Teranuma H., Katayama T., Tamanyu M., Negoro T., Satoh K., and Sakagami H., Interaction between dental metals and antioxidants assessed by cytotoxicity assay and ESR spectroscopy, Anticancer Research. (2002) 22, 4017–4022, 12553026.
- 151 Sakagami H., Arakawa H., Haeda M., Satoh K., Kadofuku T., Fukuchi K., and Gomi K., Production of hydrogen peroxide and methionine sulfoxide by epigallactocatechin gallate and antioxidants, Anticancer Research. (2001) 21, 2633–2642, 11724332.
- 152 Vojdani A., Bazargan M., Vojdani E., and Wright J., New evidence for antioxidant properties of vitamin C, Cancer Detection and Prevention. (2000) 24, no. 6, 508–523, 11198264.
- 153 Kelley E. E., Domann F. E., Buettner G. R., Oberley L. W., and 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, 9372616.
- 154
Noto V.,
Taper H. S.,
Jiang Y.-H.,
Janssens J.,
Bonte J., and
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, 2914296.
10.1002/1097-0142(19890301)63:5<901::AID-CNCR2820630518>3.0.CO;2-G CAS PubMed Web of Science® Google Scholar
- 155 Leveille C. R. and 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, 6131046.
- 156 Harada T., Enomoto A., Kitazawa T., Maita K., and 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, 3603964, https://doi.org/10.1177/030098588702400310.
- 157 Prochazkova D., Bousova I., and Wilhelmova N., Antioxidant and prooxidant properties of flavonoids, Fitoterapia. (2011) 82, 513–523, 21277359, https://doi.org/10.1016/j.fitote.2011.01.018, 2-s2.0-79955473013.
- 158 Park E. J. and Pezzuto J. M., Flavonoids in cancer prevention, Anti-Cancer Agents in Medicinal Chemistry. (2012) 12, 836–851, 22292763.
- 159 Hodnick W. F., Milosavljevic E. B., Nelson J. H., and 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, 3390220.
- 160 Choi S. I., Jeong C. S., Cho S. Y., and 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, 18038912.
- 161 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, 16276977.
- 162 Alhosin M., Leon-Gonzalez A. J., Dandache I., Lelay A., Rashid S. K., Kevers C., Pincemail J., Fornecker L. M., Mauvieux L., Herbrecht R., and Schini-Kerth V. B., 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, 25757575, https://doi.org/10.1038/srep08996, 2-s2.0-84924908487.
- 163 Kim J. H., Auger C., Kurita I., Anselm E., Rivoarilala L. O., Lee H. J., Lee K. W., and Schini-Kerth V. B., 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, 23973200, https://doi.org/10.1016/j.niox.2013.08.002, 2-s2.0-84883547986.
- 164 Sharif T., Stambouli M., Burrus B., Emhemmed F., Dandache I., Auger C., Etienne-Selloum N., Schini-Kerth V. B., and Fuhrmann G., 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.
- 165 Wang J., Lu M. L., Dai H. L., Zhang S. P., Wang H. X., and 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, 25517918, https://doi.org/10.1590/1414-431X20144074, 2-s2.0-84924908431.
- 166 Yang J., Xiao Y. L., He X. R., Qiu G. F., and 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, 20390763, https://doi.org/10.1080/10286020903427336, 2-s2.0-77951474131.
- 167 Liang T., Zhang X., Xue W., Zhao S., Zhang X., and 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, 25198898, https://doi.org/10.3390/ijms150915754, 2-s2.0-84908351148.
- 168 Lambert J. D. and 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, 20558130, https://doi.org/10.1016/j.abb.2010.06.013, 2-s2.0-77956178353.
- 169 Hwang J. T., Ha J., Park I. J., Lee S. K., Baik H. W., Kim Y. M., and Park O. J., Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway, Cancer Letters. (2007) 247, 115–121, 16797120, https://doi.org/10.1016/j.canlet.2006.03.030, 2-s2.0-33845789994.
- 170 Oikawa S., Furukawaa A., Asada H., Hirakawa K., and 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, 14567448.
- 171 Palit S., Kar S., Sharma G., and 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, 25204891, https://doi.org/10.1002/jcp.24818, 2-s2.0-84928393491.
- 172 Zhang Q., Cheng G., Qiu H., Zhu L., Ren Z., Zhao W., Zhang T., and Liu L., 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, 25820747, https://doi.org/10.1039/c5fo00142k, 2-s2.0-84929455629.
- 173 Kim G. T., Lee S. H., and 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, 25337554.
- 174 Iwasaki M., Inoue M., Otani T., Sasazuki S., Kurahashi N., Miura T., Yamamoto S., Tsugane S., and Japan Public Health Center-based Prospective Study Group, 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, 18316793, https://doi.org/10.1200/JCO.2007.13.9964, 2-s2.0-43249092642.
- 175 Jin S., Zhang Q. Y., Kang X. M., Wang J. X., and Zhao W. H., Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway, Annals of Oncology. (2010) 21, 263–268, 19889614, https://doi.org/10.1093/annonc/mdp499, 2-s2.0-77950821063.
- 176 Lo Y.-L., Wang W., and 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, 22914566, https://doi.org/10.1016/j.tox.2012.08.003, 2-s2.0-84897124002.
- 177 Yang X. J., Belosay A., Hartman J. A., Song H. X., Zhang Y. K., Wang W. D., Doerge D. R., and Helferich W. G., 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, 25749878, https://doi.org/10.1007/s10585-015-9709-2, 2-s2.0-84939967310.
- 178 Rakshit S., Mandal L., Pal B. C., Bagchi J., Biswas N., Chaudhuri J., Chowdhury A. A., Manna A., Chaudhuri U., Konar A., Mukherjee T., Jaisankar P., and Bandyopadhyay S., Involvement of ROS in chlorogenic acid-induced apoptosis of Bcr-Abl+ CML cells, Biochemical Pharmacology. (2010) 80, 1662–1675, 20832390, https://doi.org/10.1016/j.bcp.2010.08.013, 2-s2.0-77957904354.
- 179 Kim K. K., Singh A. P., Singh R. K., DeMartino A., Brard L., Vorsa N., Lange T. S., and Moore R. G., Anti-angiogenic activity of cranberry proanthocyanidins and cytotoxic properties in ovarian cancer cells, International Journal of Oncology. (2012) 40, 227–235, 21922132, https://doi.org/10.3892/ijo.2011.1198, 2-s2.0-84455193955.
- 180 Luo C., Li Y., Wang H., Cui Y., Feng Z. H., Li H., Wang Y., Wurtz K., Weber P., Long J., and Liu J., 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, 23597197.
- 181 Sun L. J., Luo C., and Liu J. K., Hydroxytyrosol induces apoptosis in human colon cancer cells through ROS generation, Food & Function. (2014) 5, 1909–1914, 24953710, https://doi.org/10.1039/c4fo00187g, 2-s2.0-84905028827.
- 182 Guha P., Dey A., Sen R., Chatterjee M., Chattopadhyay S., and 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, 20876229, https://doi.org/10.1124/jpet.110.171983, 2-s2.0-78650763353.
- 183 Alhosin M., Sharif T., Mousli M., Etienne-Selloum N., Fuhrmann G., Schini-Kerth V. B., and Bronner C., 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, 21496237, https://doi.org/10.1186/1756-9966-30-41, 2-s2.0-79955109834.
- 184 Achour M., Mousli M., Alhosin M., Ibrahim A., Peluso J., Muller C. D., Schini-Kerth V. B., Hamiche A., Dhe-Paganon S., and Bronner C., 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, 23201574, https://doi.org/10.1016/j.bbrc.2012.11.087, 2-s2.0-84872393647.
- 185 Kang J., Chen J., Shi Y., Jia J., and Zhang Y., Curcumin-induced histone hypoacetylation: the role of reactive oxygen species, Biochemical Pharmacology. (2005) 69, 1205–1213, 15794941, https://doi.org/10.1016/j.bcp.2005.01.014, 2-s2.0-15744370742.
- 186 Rajendran P., Ho E., Williams D. E., and Dashwood R. H., Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells, Clinical Epigenetics. (2011) 3, 22247744, https://doi.org/10.1186/1868-7083-3-4.
- 187 Remely M., Lovrecic L., de la Garza A. L., Migliore L., Peterlin B., Milagro F. I., Martinez A. J., and Haslberger A. G., Therapeutic perspectives of epigenetically active nutrients, British Journal of Pharmacology. (2015) 172, 2756–2768, 25046997, https://doi.org/10.1111/bph.12854, 2-s2.0-84929208390.
- 188 Vanden Berghe W., Epigenetic impact of dietary polyphenols in chemoprevention: lifelong remodeling of our epigenomes, Pharmacological Research. (2012) 65, 565–576, 22465217, https://doi.org/10.1016/j.phrs.2012.03.007, 2-s2.0-84860275721.
- 189 Malireddy S., Kotha S. R., Secor J. D., Gurney T. O., Abbott J. L., Maulik G., Maddipati K. R., and Parinandi N. L., Phytochemical antioxidants modulate mammalian ular epigenome: implications in health and disease, Antioxidants & Redox Signaling. (2012) 17, 327–339, 22404530, https://doi.org/10.1089/ars.2012.4600, 2-s2.0-84862059860.
- 190 Ong T. P., Moreno F. S., and Ross S. A., Targeting the epigenome with bioactive food components for cancer prevention, Journal of Nutrigenetics and Nutrigenomics. (2011) 4, 275–292, 22353664, https://doi.org/10.1159/000334585, 2-s2.0-84857879176.
- 191 Nakazato T., Ito K., Miyakawa Y., Kinjo K., Yamada T., Hozumi N., Ikeda Y., and Kizaki M., 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, 15749663.
- 192 Jeong J. C., Jang S. W., Kim T. H., Kwon C. H., and 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, 20358478, https://doi.org/10.1080/01635580903441287, 2-s2.0-77951116812.
- 193 Dent P., Yacoub A., Contessa J., Caron R., Amorino G., Valerie K., Hagan M. P., Grant S., and Schmidt-Ullrich R., Stress and radiation-induced activation of multiple intracellular signaling pathways, Radiation Research. (2003) 159, no. 3, 283–300, 12600231.
- 194 Mladenov E., Magin S., Soni A., and 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, 27016036, https://doi.org/10.1016/j.semcancer.2016.03.003, 2-s2.0-84969262470.
- 195 Roos W. P., Thomas A. D., and Kaina B., DNA damage and the balance between survival and death in cancer biology, Nature Reviews Cancer. (2016) 16, no. 1, 20–33, 26678314, https://doi.org/10.1038/nrc.2015.2, 2-s2.0-84952637939.
- 196 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, 3065826.
- 197 O’Driscoll M. and Jeggo P. A., The role of double-strand break repair—insights from human genetics, Nature Reviews Genetics. (2006) 7, no. 1, 45–54, 16369571, https://doi.org/10.1038/nrg1746, 2-s2.0-29244437908.
- 198 Jackson S. P. and Bartek J., The DNA-damage response in human biology and disease, Nature. (2009) 461, no. 7267, 1071–1078, 19847258, https://doi.org/10.1038/nature08467, 2-s2.0-70350504453.
- 199 Tubiana M., The role of local treatment in the cure of cancer, European Journal of Cancer. (1992) 28A, 2061–2069, 1419303.
