Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies

Life Sciences - Tập 148 - Trang 183-193 - 2016
Vibha Rani1, Gagan Deep2, Rakesh K. Singh3, Komaraiah Palle4, Umesh C. S. Yadav5
1Department of Biotechnology, JayPee Institute of Information Technology, A-10, Sector-62, Noida 201 307, UP, India
2Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, 12850 E. Montview Blvd, Aurora, CO 80045, USA
3Translational Science Laboratory, College of Medicine, Florida State University, 1115 West Call St., Tallahassee, FL 32306-4300, USA
4Department of Oncologic Sciences, USA Mitchell Cancer Institute, 1660 Spring Hill Avenue, Mobile, AL 36604, USA
5Metabolic Disorder & Inflammatory Pathologies Laboratory, School of Life Sciences, Central University of Gujarat, Gandhinagar 382030, India

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Braun, 2011, The link between the metabolic syndrome and cancer, Int. J. Biol. Sci., 7, 1003, 10.7150/ijbs.7.1003

NHLBI Website: http://www.nhlbi.nih.gov/health/health-topics/topics/ms (accessed Jan 14, 2016).

WHO website: http://www.who.int/mediacentre/factsheets/fs311/en/ (accessed Jan 14, 2016).

Ng, 2014, Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the global burden of disease study 2013, Lancet, 384, 766, 10.1016/S0140-6736(14)60460-8

Ford, 2002, Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey, J. Am. Med. Assoc., 287, 356, 10.1001/jama.287.3.356

Calle, 2003, Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults, N. Engl. J. Med., 348, 1625, 10.1056/NEJMoa021423

Gallagher, 2010, 579

Gallagher, 2010, The pathway from diabetes and obesity to cancer, on the route to targeted therapy, Endocr. Pract., 16, 864, 10.4158/EP10098.RA

Gandhi, 2012, Assessment of DNA damage in obese individuals, Res. J. Biol., 2, 37

Al-Aubaidy, 2011, Oxidative DNA damage and obesity in type-2 diabetes mellitus, Eur. J. Endocrinol., 164, 899, 10.1530/EJE-11-0053

Reuter, 2010, Oxidative stress, inflammation, and cancer: how are they linked?, Free Radic. Biol. Med., 49, 1603, 10.1016/j.freeradbiomed.2010.09.006

Furukawa, 2004, Increased oxidative stress in obesity and its impact on metabolic syndrome, J. Clin. Invest., 114, 1752, 10.1172/JCI21625

Hansel, 2004, Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity, J. Clin. Endocrinol. Metab., 89, 4963, 10.1210/jc.2004-0305

Holvoet, 2008, Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease, Verh. K. Acad. Geneeskd. Belg., 70, 193

Marques de Mattos, 2012, Protein oxidative stress and dyslipidemia in dialysis patients, Ther. Apher. Dial., 16, 68, 10.1111/j.1744-9987.2011.01009.x

Zelzer, 2011, High density lipoprotein cholesterol level is a robust predictor of lipid peroxidation irrespective of gender, age, obesity, and inflammatory or metabolic biomarkers, Clin. Chim. Acta, 412, 1345, 10.1016/j.cca.2011.03.031

Holvoet, 2004, The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in well-functioning elderly people in the health, aging, and body composition cohort, Diabetes, 53, 1068, 10.2337/diabetes.53.4.1068

Fortuño, 2006, Phagocytic NADPH oxidase overactivity underlies oxidative stress in metabolic syndrome, Diabetes, 55, 209, 10.2337/diabetes.55.01.06.db05-0751

Murphy, 2009, How mitochondria produce reactive oxygen species, Biochem. J., 417, 1, 10.1042/BJ20081386

Balaban, 2005, Mitochondria, oxidants, and aging, Cell, 120, 483, 10.1016/j.cell.2005.02.001

Hutcheson, 2012, The metabolic syndrome, oxidative stress, environment, and cardiovascular disease: the great exploration, Exp. Diabetes Res., 2012, 1, 10.1155/2012/271028

Davì, 1999, In vivo formation of 8-iso-prostaglandin f2 alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation, Circulation, 99, 224, 10.1161/01.CIR.99.2.224

Grattagliano, 2008, Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis, J. Nutr. Biochem., 19, 491, 10.1016/j.jnutbio.2007.06.011

Yadav, 2015, Cysteinyl leukotrienes (CysLTs): role in obesity-induced asthma, Curr. Mol. Med., 15, 598, 10.2174/1566524015666150831130954

Jiang, 2011, Systemic upregulation of NADPH oxidase in diet-induced obesity in rats, Redox Rep., 16, 223, 10.1179/174329211X13049558293713

Beckman, 1996, Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly, Am. J. Physiol., 271, C1424, 10.1152/ajpcell.1996.271.5.C1424

Huang, 2005, Unraveling the links between diabetes, obesity, and cardiovascular disease, Circ. Res., 96, 1129, 10.1161/01.RES.0000170705.56583.45

Shishehbor, 2003, Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy, JAMA, 289, 1675, 10.1001/jama.289.13.1675

Ma, 2013, Obesity and risk of colorectal cancer: a systematic review of prospective studies, PLoS One, 8, 10.1371/journal.pone.0053916

Li, 2015, Relationship between body mass index and incidence of breast cancer, Int. J. Clin. Exp. Med., 8, 11549

De Pergola, 2013, Obesity as a major risk factor for cancer, J. Obes., 2013, 291546, 10.1155/2013/291546

van Kruijsdijk, 2009, Obesity and cancer: the role of dysfunctional adipose tissue, Cancer Epidemiol. Biomark. Prev., 18, 2569, 10.1158/1055-9965.EPI-09-0372

Fernández-Sánchez, 2011, Inflammation, oxidative stress, and obesity, Int. J. Mol. Sci., 12, 3117, 10.3390/ijms12053117

Khandrika, 2009, Oxidative stress in prostate cancer, Cancer Lett., 282, 125, 10.1016/j.canlet.2008.12.011

Grek, 2010, Redox metabolism and malignancy, Curr. Opin. Pharmacol., 10, 362, 10.1016/j.coph.2010.05.003

Kumar, 2008, Oxidative stress is B inherent in prostate cancer cells and is required for aggressive phenotype, Cancer Res., 68, 1777, 10.1158/0008-5472.CAN-07-5259

Dröse, 2012, Molecular mechanisms of superoxide production by the mitochondrial respiratory chain, 145

Martindale, 2002, Cellular response to oxidative stress: signaling for suicide and survival, J. Cell. Physiol., 192, 1, 10.1002/jcp.10119

Gorrini, 2013, Modulation of oxidative stress as an anticancer strategy, Nat. Rev. Drug Discov., 12, 931, 10.1038/nrd4002

Dupont, 2013, Obesity leads to higher risk of sperm DNA damage in infertile patients, Asian J. Androl., 15, 622, 10.1038/aja.2013.65

Nakabeppu, 2014, Cellular levels of 8-oxoguanine in either DNA or the nucleotide pool play pivotal roles in carcinogenesis and survival of cancer cells, Int. J. Mol. Sci., 15, 12543, 10.3390/ijms150712543

Toyokuni, 1995, Persistent oxidative stress in cancer, FEBS Lett., 358, 1, 10.1016/0014-5793(94)01368-B

Dahl, 2011, Advances in DNA methylation: 5-hydroxymethylcytosine revisited, Clin. Chim. Acta, 412, 831, 10.1016/j.cca.2011.02.013

Belot, 2013, CpG methylation changes within the IL2RA promoter in type 1 diabetes of childhood onset, PLoS One, 8, 10.1371/journal.pone.0068093

Ling, 2008, Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion, Diabetologia, 51, 615, 10.1007/s00125-007-0916-5

Hall, 2013, DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human pancreatic islets, BMC Med. Genet., 14, 76, 10.1186/1471-2350-14-76

Campbell, 2013, Altered histone modifications in cancer, Adv. Exp. Med. Biol., 754, 81, 10.1007/978-1-4419-9967-2_4

Sawan, 2010, Histone modifications and cancer, Adv. Genet., 70, 57, 10.1016/B978-0-12-380866-0.60003-4

Monks, 2006, Ros-induced histone modifications and their role in cell survival and cell death, Drug Metab. Rev., 38, 755, 10.1080/03602530600959649

Afanas'ev, 2013, New nucleophilic mechanisms of ros-dependent epigenetic modifications: comparison of aging and cancer, Aging Dis., 5, 52, 10.14336/AD.2014.050052

Yahagi, 2004, p53 involvement in the pathogenesis of fatty liver disease, J. Biol. Chem., 279, 20571, 10.1074/jbc.M400884200

Tyner, 2002, p53 mutant mice that display early ageing-associated phenotypes, Nature, 415, 45, 10.1038/415045a

Vousden, 2009, p53 and metabolism, Nat. Rev. Cancer, 9, 691, 10.1038/nrc2715

Matoba, 2006, p53 regulates mitochondrial respiration, Science, 312, 1650, 10.1126/science.1126863

McNaughton, 2013, ‘Diabesity’ down under: overweight and obesity as cultural signifiers for type 2 diabetes mellitus, Crit. Public Health, 23, 274, 10.1080/09581596.2013.766671

Kaur, 2014, A comprehensive review on metabolic syndrome, Cardiol. Res. Pract., 2014, 943162, 10.1155/2014/943162

Warolin, 2013, The relationship of oxidative stress, adiposity and metabolic risk factors in healthy Black and White American youth, Pediatr. Obes., 9, 43, 10.1111/j.2047-6310.2012.00135.x

Karaouzene, 2011, Effects of the association of aging and obesity on lipids, lipoproteins and oxidative stress biomarkers: a comparison of older with young men, Nutr. Metab. Cardiovasc. Dis., 21, 792, 10.1016/j.numecd.2010.02.007

Savini, 2013, Obesity-associated oxidative stress: strategies finalized to improve redox state, Int. J. Mol. Sci., 14, 10497, 10.3390/ijms140510497

Codoñer-Franch, 2012, Elevated advanced oxidation protein products (AOPPs) indicate metabolic risk in severely obese children, Nutr. Metab. Cardiovasc. Dis., 22, 237, 10.1016/j.numecd.2010.06.002

Sies, 2005, Nutritional, dietary and postprandial oxidative stress, J. Nutr., 135, 969, 10.1093/jn/135.5.969

Dandona, 2010, Macronutrient intake induces oxidative and inflammatory stress: potential relevance to atherosclerosis and insulin resistance, Exp. Mol. Med., 42, 245, 10.3858/emm.2010.42.4.033

Lee, 2009, Reactive oxygen species facilitate adipocyte differentiation by accelerating mitotic clonal expansion, J. Biol. Chem., 284, 10601, 10.1074/jbc.M808742200

Tormos, 2011, Mitochondrial complex III ROS regulate adipocyte differentiation, Cell Metab., 14, 537, 10.1016/j.cmet.2011.08.007

Fajas, 2003, Adipogenesis: a cross-talk between cell proliferation and cell differentiation, Ann. Med., 35, 79, 10.1080/07853890310009999

Schröder, 2009, Nox4 acts as a switch between differentiation and proliferation in preadipocytes, Arterioscler. Thromb. Vasc. Biol., 29, 239, 10.1161/ATVBAHA.108.174219

Kanda, 2011, Reactive oxygen species mediate adipocyte differentiation in mesenchymal stem cells, Life Sci., 89, 250, 10.1016/j.lfs.2011.06.007

Monteiro, 2010, Chronic inflammation in obesity and the metabolic syndrome, Mediat. Inflamm., 2010, 289645, 10.1155/2010/289645

Malandrino, 2015, Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation, Am. J. Physiol. Endocrinol. Metab., 308, E756, 10.1152/ajpendo.00362.2014

Inoue, 2008, Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity, and insulin resistance, J. Biol. Chem., 283, 21220, 10.1074/jbc.M801824200

Macleod, 2008, The role of the RB tumour suppressor pathway in oxidative stress responses in the haematopoietic system, Nat. Rev. Cancer, 8, 769, 10.1038/nrc2504

Fajas, 2002, E2Fs regulate adipocyte differentiation, Dev. Cell, 3, 39, 10.1016/S1534-5807(02)00190-9

Richon, 1997, Regulation and expression of retinoblastoma proteins p107 and p130 during 3T3-L1 adipocyte differentiation, J. Biol. Chem., 272, 10117, 10.1074/jbc.272.15.10117

Wang, 2015, Mitochondrial reactive oxygen species regulate adipocyte differentiation of mesenchymal stem cells in hematopoietic stress induced by arabinosylcytosine, PLoS One, 10

Patel, 2007, Prolonged reactive oxygen species generation and nuclear factor-kappaB activation after a high-fat, high-carbohydrate meal in the obese, J. Clin. Endocrinol. Metab., 92, 4476, 10.1210/jc.2007-0778

Bondia-Pons, 2012, Oxidative stress and inflammation interactions in human obesity, J. Physiol. Biochem., 68, 701, 10.1007/s13105-012-0154-2

Chrysohoou, 2007, The implication of obesity on total antioxidant capacity in apparently healthy men and women: the ATTICA study, Nutr. Metab. Cardiovasc. Dis., 17, 590, 10.1016/j.numecd.2006.05.007

Bryan, 2013, Redox-inflammatory synergy in the metabolic syndrome, Can. J. Physiol. Pharmacol., 91, 22, 10.1139/cjpp-2012-0295

Dandona, 2005, Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation, Circulation, 111, 1448, 10.1161/01.CIR.0000158483.13093.9D

Houstis, 2006, Reactive oxygen species have a causal role in multiple forms of insulin resistance, Nature, 440, 944, 10.1038/nature04634

Matsuzawa-Nagata, 2008, Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity, Metabolism, 57, 1071, 10.1016/j.metabol.2008.03.010

Kunitomo, 2008, Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome, J. Pharmacol. Sci., 107, 128, 10.1254/jphs.FP0072365

Boden, 1997, Role of fatty acids in the pathogenesis of insulin resistance and NIDDM, Diabetes, 46, 3, 10.2337/diab.46.1.3

Cohen, 1996, Modulation of insulin activities by leptin, Science, 274, 1185, 10.1126/science.274.5290.1185

Wojtczak, 1993, Effect of fatty acids on energy coupling processes in mitochondria, Biochim. Biophys. Acta, 1183, 41, 10.1016/0005-2728(93)90004-Y

Lenzen, 1996, Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues, Free Radic. Biol. Med., 20, 463, 10.1016/0891-5849(96)02051-5

Swenne, 1983, Effects of aging on the regenerative capacity of the pancreatic B-cell of the rat, Diabetes, 32, 14, 10.2337/diab.32.1.14

Mares, 1993, Expression of certain antiproliferative and growth-related genes in isolated mouse pancreatic islets: analysis by polymerase chain reaction, Diabète Métab., 19, 315

Chetboun, 2012, Maintenance of redox state and pancreatic beta-cell function: role of leptin and adiponectin, J. Cell. Biochem., 113, 1966, 10.1002/jcb.24065

Rane, 1999, Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia, Nat. Genet., 22, 44, 10.1038/8751

Cozar-Castellano, 2004, Induction of beta-cell proliferation and retinoblastoma protein phosphorylation in rat and human islets using adenovirus-mediated transfer of cyclin-dependent kinase-4 and cyclin D1, Diabetes, 53, 149, 10.2337/diabetes.53.1.149

Fatrai, 2006, Akt induces beta-cell proliferation by regulating cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 activity, Diabetes, 55, 318, 10.2337/diabetes.55.02.06.db05-0757

Fiaschi-Taesch, 2013, Human pancreatic β-cell G1/S molecule cell cycle atlas, Diabetes, 62, 2450, 10.2337/db12-0777

Sciacovelli, 2014, The metabolic alterations of cancer cells, Methods Enzymol., 542, 1, 10.1016/B978-0-12-416618-9.00001-7

Ceriello, 1993, Diabetes mellitus and hypertension: the possible role of hyperglycaemia through oxidative stress, Diabetologia, 36, 265, 10.1007/BF00399961

Wolff, 1991, Protein glycation and oxidative stress in diabetes mellitus and ageing, Free Radic. Biol. Med., 10, 339, 10.1016/0891-5849(91)90040-A

Medema, 2000, AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1, Nature, 404, 782, 10.1038/35008115

Schmidt, 2002, Cell cycle inhibition by FoxO forkhead transcription factors involves downregulation of cyclin D, Mol. Cell. Biol., 22, 7842, 10.1128/MCB.22.22.7842-7852.2002

Nakamura, 2000, Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN, Mol. Cell. Biol., 20, 8969, 10.1128/MCB.20.23.8969-8982.2000

Furukawa-Hibi, 2002, FOXO forkhead transcription factors induce G(2)-M checkpoint in response to oxidative stress, J. Biol. Chem., 277, 26729, 10.1074/jbc.C200256200

Szczepaniak, 2003, Myocardial triglycerides and systolic function in humans: in vivo evaluation by localized proton spectroscopy and cardiac imaging, Magn. Reson. Med., 49, 417, 10.1002/mrm.10372

Ilkun, 2013, Cardiac dysfunction and oxidative stress in the metabolic syndrome: an update on antioxidant therapies, Curr. Pharm. Des., 19, 4806, 10.2174/1381612811319270003

Shibata, 2009, Adiponectin and cardiovascular disease, Circ. J., 73, 608, 10.1253/circj.CJ-09-0057

Singh, 2002, Pathogenesis of atherosclerosis: a multifactorial process, Exp. Clin. Cardiol., 7, 40

Aprahamia, 2011, Adiponectin in cardiovascular inflammation and obesity, Int. J. Inflamm., 2011, 376909

Kohli, 2013, Curcumin suppresses gelatinase B mediated norepinephrine induced stress in H9c2 cardiomyocytes, PLoS One, 8, 10.1371/journal.pone.0076519

Atale, 2013, Cardioprotective role of Syzygium cumini against glucose-induced oxidative stress in H9C2 cardiac myocytes, Cardiovasc. Toxicol., 13, 278, 10.1007/s12012-013-9207-1

Jain, 2015, An assessment of norepinephrine mediated hypertrophy to apoptosis transition in cardiac cells: a signal for cell death, Chem. Biol. Interact., 225, 54, 10.1016/j.cbi.2014.11.017

Karasu, 2010, Glycoxidative stress and cardiovascular complications in experimentally-induced diabetes: effects of antioxidant treatment, Open Cardiovasc. Med. J., 4, 240, 10.2174/1874192401004010240

Giacco, 2010, Oxidative stress and diabetic complications, Circ. Res., 107, 1058, 10.1161/CIRCRESAHA.110.223545

Yamagishi, 2012, Role of advanced glycation end products (AGEs) and oxidative stress in vascular complications in diabetes, Biochim. Biophys. Acta, 1820, 663, 10.1016/j.bbagen.2011.03.014

Bitar, 2005, Nitric oxide dynamics and endothelial dysfunction in type II model of genetic diabetes, Eur. J. Pharmacol., 511, 53, 10.1016/j.ejphar.2005.01.014

Pechánová, 2015, Cardiac NO signalling in the metabolic syndrome, Br. J. Pharmacol., 172, 1415, 10.1111/bph.12960

Endemann, 2004, Nitric oxide, oxidative excess, and vascular complications of diabetes mellitus, Curr. Hypertens. Rep., 6, 85, 10.1007/s11906-004-0081-x

Hotamisligil, 2006, Inflammation and metabolic disorders, Nature, 444, 860, 10.1038/nature05485

Ndisang, 2014, Oxidative stress and inflammation in obesity, diabetes, hypertension, and related cardiometabolic complications, Oxidative Med. Cell. Longev., 2014, 506948, 10.1155/2014/506948

Ho, 2013, Biological markers of oxidative stress: applications to cardiovascular research and practice, Redox Biol., 1, 483, 10.1016/j.redox.2013.07.006

Mesquita, 2010, Reactive oxygen species mediate mitogenic growth factor signaling pathways in human leiomyoma smooth muscle cells, Biol. Reprod., 82, 341, 10.1095/biolreprod.108.075887

Li, 1997, Differential effect of hydrogen peroxide and superoxide anion on apoptosis and proliferation of vascular smooth muscle cells, Circulation, 96, 3602, 10.1161/01.CIR.96.10.3602

Rao, 1992, Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression, Circ. Res., 70, 593, 10.1161/01.RES.70.3.593

Paravicini, 2006, Redox signaling in hypertension, Cardiovasc. Res., 71, 247, 10.1016/j.cardiores.2006.05.001

Fu, 2007, Non-genomic effects of 17beta-estradiol in activation of the ERK1/ERK2 pathway induces cell proliferation through upregulation of cyclin D1 expression in bovine artery endothelial cells, Gynecol. Endocrinol., 23, 131, 10.1080/09513590601181457

Burch, 2005, Redox regulation of cell-cycle re-entry: cyclin D1 as a primary target for the mitogenic effects of reactive oxygen and nitrogen species, Antioxid. Redox Signal., 7, 741, 10.1089/ars.2005.7.741

He, 2003, Redox factor-1 contributes to the regulation of progression from G0/G1 to S by PDGF in vascular smooth muscle cells, Am. J. Physiol. Heart Circ. Physiol., 285, H804, 10.1152/ajpheart.01080.2002

Qin, 2014, Inhibition of smooth muscle cell proliferation by ezetimibe via the cyclin D1-MAPK pathway, J. Pharmacol. Sci., 125, 283, 10.1254/jphs.13239FP

Park, 2015, Scoparone interferes with STAT3-induced proliferation of vascular smooth muscle cells, Exp. Mol. Med., 47, 10.1038/emm.2014.113

Mathew, 2014, Involvement of the antioxidant effect and anti-inflammatory response in butyrate-inhibited vascular smooth muscle cell proliferation, Pharm. Basel Switz., 7, 1008

Bigornia, 2010, Long-term successful weight loss improves vascular endothelial function in severely obese individuals, Obesity (Silver Spring), 18, 754, 10.1038/oby.2009.482

Sofi, 2010, Accruing evidence on benefits of adherence to the Mediterranean diet on health: An updated systematic review and meta-analysis, Am. J. Clin. Nutr., 92, 1189, 10.3945/ajcn.2010.29673

Arora, 2013, Probiotics: interaction with gut microbiome and antiobesity potential, Nutrition, 29, 591, 10.1016/j.nut.2012.07.017

Mente, 2009, A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease, Arch. Intern. Med., 169, 659, 10.1001/archinternmed.2009.38

González-Castejón, 2011, Dietary phytochemicals and their potential effects on obesity: a review, Pharmacol. Res., 64, 438, 10.1016/j.phrs.2011.07.004

Calder, 2011, Dietary factors and low-grade inflammation in relation to overweight and obesity, Br. J. Nutr., 106, S5, 10.1017/S0007114511005460

Bjelakovic, 2012, Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases, Cochrane Database Syst. Rev., 3, 10.1002/14651858.CD007176.pub2

Lin, 2009, Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial, J. Natl. Cancer Inst., 10, 14, 10.1093/jnci/djn438

Sinha, 2014, Antidiabetic potential of herbal plants and polyherbal formulation, Int. J. Phytother. Res., 4, 28

Scheele, 2009, ROS and myokines promote muscle adaptation to exercise, Trends Endocrinol. Metab., 20, 95, 10.1016/j.tem.2008.12.002

Kramer, 2007, Exercise, MAPK, and NF-κB signaling in skeletal muscle, J. Appl. Physiol., 103, 388, 10.1152/japplphysiol.00085.2007

Cairns, 2013, Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities, Cancer Discov., 3, 730, 10.1158/2159-8290.CD-13-0083

Shrotriya, 2015, Grape seed extract targets mitochondrial electron transport chain complex III and induces oxidative and metabolic stress leading to cytoprotective autophagy and apoptotic death in human head and neck cancer cells, Mol. Carcinog., 54, 1734, 10.1002/mc.22246

Kim, 2015, Cancer metabolism: strategic diversion from targeting cancer drivers to targeting cancer suppliers, Biomol. Ther., 23, 99, 10.4062/biomolther.2015.013

Rysman, 2010, De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation, Cancer Res., 70, 8117, 10.1158/0008-5472.CAN-09-3871

Chen, 2012, Prevention of obesity-associated colon cancer by (−)-epigallocatechin-3 gallate and curcumin, Trans. Gastrointest. Cancer, 1, 243

Lee, 2012, Metformin use is associated with a decreased incidence of colorectal adenomas in diabetic patients with previous colorectal cancer, Dig. Liver Dis., 44, 1042, 10.1016/j.dld.2012.06.007

Kim, 2015, Inhibitory effect of metformin therapy on the incidence of colorectal advanced adenomas in patients with diabetes, Intest. Res., 13, 145, 10.5217/ir.2015.13.2.145

Provinciali, 2015, Metformin: risk–benefit profile with a focus on cancer, Expert Opin. Drug Saf., 14, 1, 10.1517/14740338.2015.1084289

Belda-Iniesta, 2011, Metformin: a new option in cancer treatment, Clin. Transl. Oncol., 13, 363, 10.1007/s12094-011-0669-y

Lonardo, 2013, Metformin targets the metabolic achilles heel of human pancreatic cancer stem cells, PLoS One, 8, 10.1371/journal.pone.0076518

Rizos, 2013, Metformin and cancer, Eur. J. Pharmacol., 705, 96, 10.1016/j.ejphar.2013.02.038

Guppy, 2011, Anticancer effects of metformin and its potential use as a therapeutic agent for breast cancer, Future Oncol., 7, 727, 10.2217/fon.11.49

Quinn, 2013, Repositioning metformin for cancer prevention and treatment, Trends Endocrinol. Metab., 24, 469, 10.1016/j.tem.2013.05.004

Malazy, 2015, Targeting metabolic disorders by natural products, J. Diabetes Metab. Disord., 14, 57, 10.1186/s40200-015-0184-8

Eddouks, 2012, Medicinal plants in the prevention and treatment of chronic diseases, Evid. Based Complement. Alternat. Med., 2012, 1

Pandey, 2009, Plant polyphenols as dietary antioxidants in human health and disease, Oxidative Med. Cell. Longev., 2, 270, 10.4161/oxim.2.5.9498

Parasuraman, 2014, Polyherbal formulation: concept of Ayurveda, Pharmacogn. Rev., 8, 73, 10.4103/0973-7847.134229

Saxena, 2013, Phytochemistry of medicinal plants, J. Pharmacogn. Phytochem., 1, 168