{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:02:23Z","timestamp":1791298943865,"version":"4.1.0"},"reference-count":127,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2016R1D1A1B010"],"award-info":[{"award-number":["2016R1D1A1B010"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The relationship between colitis-associated colorectal cancer (CAC) and the dysregulation of iron metabolism has been implicated. However, studies on the influence of dietary iron deficiency on the incidence of CAC are limited. This study investigated the effects of dietary iron deficiency and dietary non-heme iron on CAC development in an azoxymethane\/dextran sodium sulfate (AOM\/DSS) mouse model. The four-week-old mice were divided into the following groups: iron control (IC; 35 ppm iron\/kg) + normal (NOR), IC + AOM\/DSS, iron deficient (ID; &lt;5 ppm iron\/kg diet) + AOM\/DSS, and iron overload (IOL; approximately 2000 ppm iron\/kg) + AOM\/DSS. The mice were fed the respective diets for 13 weeks, and the AOM\/DSS model was established at week five. FTH1 expression increased in the mice\u2019s colons in the IC + AOM\/DSS group compared with that observed in the ID and IOL + AOM\/DSS groups. The reduced number of colonic tumors in the ID + AOM\/DSS and IOL + AOM\/DSS groups was accompanied by the downregulated expression of cell proliferation regulators (PCNA, cyclin D1, and c-Myc). Iron overload inhibited the increase in the expression of NF-\u03baB and its downstream inflammatory cytokines (IL-6, TNF\u03b1, iNOS, COX2, and IL-1\u03b2), likely due to the elevated expression of antioxidant genes (SOD1, TXN, GPX1, GPX4, CAT, HMOX1, and NQO1). ID + AOM\/DSS may hinder tumor development in the AOM\/DSS model by inhibiting the PI3K\/AKT pathway by increasing the expression of Ndrg1. Our study suggests that ID and IOL diets suppress AOM\/DSS-induced tumors and that long-term iron deficiency or overload may negate CAC progression.<\/jats:p>","DOI":"10.3390\/nu14102033","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T21:46:53Z","timestamp":1652392013000},"page":"2033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Supplementation with High or Low Iron Reduces Colitis Severity in an AOM\/DSS Mouse Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Seonghwan","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4036-4661","authenticated-orcid":false,"given":"Yeonhee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3443-5286","authenticated-orcid":false,"given":"Seungmin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR Project, College of Human Ecology, Yonsei University, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41392-020-0116-z","article-title":"Comprehensive review of targeted therapy for colorectal cancer","volume":"5","author":"Xie","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1055\/s-0037-1602237","article-title":"Colorectal cancer in inflammatory bowel disease","volume":"31","author":"Stidham","year":"2018","journal-title":"Clin. Colon Rectal Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S2468-1253(17)30004-3","article-title":"Risk of colorectal cancer in Asian patients with ulcerative colitis: A systematic review and meta-analysis","volume":"2","author":"Bopanna","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.autrev.2017.02.013","article-title":"IBD immunopathogenesis: A comprehensive review of inflammatory molecules","volume":"16","author":"Park","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.gtc.2006.07.002","article-title":"Molecular biology of dysplasia and cancer in inflammatory bowel disease","volume":"35","author":"Itzkowitz","year":"2006","journal-title":"Gastroenterol. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/MEG.0b013e32835b5803","article-title":"Overview of molecular pathways in inflammatory bowel disease associated with colorectal cancer development","volume":"25","author":"Azer","year":"2013","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.coph.2009.06.006","article-title":"Inflammation and colorectal cancer","volume":"9","author":"Kraus","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.blre.2008.08.001","article-title":"Ferritin for the clinician","volume":"23","author":"Knovich","year":"2009","journal-title":"Blood Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1111\/hdi.12542","article-title":"Overview of iron metabolism in health and disease","volume":"21","author":"Dev","year":"2017","journal-title":"Hemodial. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1559S","DOI":"10.3945\/ajcn.117.155804","article-title":"Current understanding of iron homeostasis","volume":"106","author":"Anderson","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1177\/0148607112459648","article-title":"Iron metabolism in man","volume":"37","author":"Adamson","year":"2013","journal-title":"J. Parenter. Enter. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1039\/C7MT00143F","article-title":"The transferrin receptor: The cellular iron gate","volume":"9","author":"Gammella","year":"2017","journal-title":"Metallomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/nyas.13008","article-title":"Iron and cancer: Recent insights","volume":"1368","author":"Manz","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Forciniti, S., Greco, L., Grizzi, F., Malesci, A., and Laghi, L. (2020). Iron metabolism in cancer progression. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062257"},{"key":"ref_16","first-page":"503","article-title":"Iron intake and the risk of colorectal cancer","volume":"5","author":"Wurzelmann","year":"1996","journal-title":"Cancer Epidemiol. Prev. Biomark."},{"key":"ref_17","first-page":"1029","article-title":"Dietary iron and recurrence of colorectal adenomas","volume":"6","author":"Tseng","year":"1997","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1111\/jgh.14642","article-title":"Association between dietary iron and zinc intake and development of ulcerative colitis: A case\u2013control study in Japan","volume":"34","author":"Kobayashi","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1207\/s15327914nc4901_9","article-title":"High Dietary Iron and Copper and Risk of Colorectal Cancer: A Case-Control Study in Burgundy, France","volume":"49","author":"Senesse","year":"2004","journal-title":"Nutr. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shivappa, N., Godos, J., H\u00e9bert, J.R., Wirth, M.D., Piuri, G., Speciani, A.F., and Grosso, G. (2017). Dietary Inflammatory Index and Colorectal Cancer Risk\u2014A Meta-Analysis. Nutrients, 9.","DOI":"10.3390\/nu9091043"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1097\/MIB.0000000000001161","article-title":"Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn\u2019s Disease and Ulcerative Colitis","volume":"23","author":"Khalili","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S2468-1253(19)30294-8","article-title":"Modifiable pathways for colorectal cancer: A mendelian randomisation analysis","volume":"5","author":"Cornish","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/sj.bjc.6603837","article-title":"A cohort study of dietary iron and heme iron intake and risk of colorectal cancer in women","volume":"97","author":"Kabat","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mahalhal, A., Burkitt, M.D., Duckworth, C.A., Hold, G.L., Campbell, B.J., Pritchard, D.M., and Probert, C.S. (2021). Long-Term Iron Deficiency and Dietary Iron Excess Exacerbate Acute Dextran Sodium Sulphate-Induced Colitis and Are Associated with Significant Dysbiosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073646"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1023\/A:1015362228659","article-title":"Dietary Iron Supplementation Enhances DSS-Induced Colitis and Associated Colorectal Carcinoma Development in Mice","volume":"47","author":"Seril","year":"2002","journal-title":"Dig. Dis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/carcin\/24.3.353","article-title":"Oxidative stress and ulcerative colitis-associated carcinogenesis: Studies in humans and animal models","volume":"24","author":"Seril","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yilmaz, B., and Li, H. (2018). Gut Microbiota and Iron: The Crucial Actors in Health and Disease. Pharmaceuticals, 11.","DOI":"10.3390\/ph11040098"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1080\/10408398.2012.749208","article-title":"Dietary Iron and Colorectal Cancer Risk: A Review of Human Population Studies","volume":"56","author":"Ashmore","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/mi.2010.62","article-title":"Reactive oxygen species mediate inflammatory cytokine release and EGFR-dependent mucin secretion in airway epithelial cells exposed to Pseudomonas pyocyanin","volume":"4","author":"Rada","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/1319-3767.173753","article-title":"The implications of oxidative stress and antioxidant therapies in Inflammatory Bowel Disease: Clinical aspects and animal models","volume":"22","author":"Balmus","year":"2016","journal-title":"Saudi J. Gastroenterol. Off. J. Saudi Gastroenterol. Assoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.freeradbiomed.2010.09.006","article-title":"Oxidative stress, inflammation, and cancer: How are they linked?","volume":"49","author":"Reuter","year":"2010","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1046\/j.1365-2036.2000.00828.x","article-title":"Effects of iron and iron chelation in vitro on mucosal oxidant activity in ulcerative colitis","volume":"14","author":"Millar","year":"2000","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1046\/j.1365-2036.2001.01113.x","article-title":"Effect of oral iron supplementation on oxidative stress and colonic inflammation in rats with induced colitis","volume":"15","author":"Carrier","year":"2001","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nielsen, O.H., Soendergaard, C., Vikner, M.E., and Weiss, G. (2018). Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease. Nutrients, 10.","DOI":"10.3390\/nu10010082"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, Y., Yu, L., Ding, J., and Chen, Y. (2019). Iron metabolism in cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010095"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.3390\/nu5072333","article-title":"Intestinal iron homeostasis and colon tumorigenesis","volume":"5","author":"Xue","year":"2013","journal-title":"Nutrients"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0140-6736(20)32594-0","article-title":"Iron deficiency","volume":"397","author":"Pasricha","year":"2021","journal-title":"Lancet"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00384-004-0588-2","article-title":"Effects of iron deprivation or chelation on DNA damage in experimental colitis","volume":"19","author":"Barollo","year":"2004","journal-title":"Int. J. Colorectal Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chua, A.C.G., Klopcic, B.R.S., Ho, D.S., Fu, S.K., Forrest, C.H., Croft, K.D., Olynyk, J.K., Lawrance, I.C., and Trinder, D. (2013). Dietary Iron Enhances Colonic Inflammation and IL-6\/IL-11-Stat3 Signaling Promoting Colonic Tumor Development in Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078850"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.3892\/ijo.2014.2259","article-title":"The IL-6\/JAK\/STAT3 pathway: Potential therapeutic strategies in treating colorectal cancer","volume":"44","author":"Wang","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41419-017-0176-3","article-title":"Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer progression through IL-6\/JAK2\/STAT3 signaling","volume":"9","author":"Zhang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1158\/1078-0432.CCR-12-2623","article-title":"PI3K\/AKT signaling is essential for communication between tissue-infiltrating mast cells, macrophages, and epithelial cells in colitis-induced cancer","volume":"19","author":"Khan","year":"2013","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41419-020-2299-1","article-title":"Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis","volume":"11","author":"Xu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_44","first-page":"1143","article-title":"Iron metabolism and its contribution to cancer","volume":"54","author":"Chen","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/cphy.c120016","article-title":"Iron homeostasis in the liver","volume":"3","author":"Anderson","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2119\/2006-00057.Fujita","article-title":"Hepcidin expression in the liver: Relatively low level in patients with chronic hepatitis C","volume":"13","author":"Fujita","year":"2007","journal-title":"Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.3390\/nu5082836","article-title":"Iron Deprivation in Cancer\u2014Potential Therapeutic Implications","volume":"5","author":"Heath","year":"2013","journal-title":"Nutrients"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.jcmgh.2016.01.006","article-title":"Critical role of PepT1 in promoting colitis-associated cancer and therapeutic benefits of the anti-inflammatory PepT1-mediated tripeptide KPV in a murine model","volume":"2","author":"Viennois","year":"2016","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_49","first-page":"76","article-title":"Bax expression is a candidate prognostic and predictive marker of colorectal cancer","volume":"1","author":"Katkoori","year":"2010","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5126048","DOI":"10.1155\/2017\/5126048","article-title":"The Role of Proinflammatory Pathways in the Pathogenesis of Colitis-Associated Colorectal Cancer","volume":"2017","author":"Luo","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hirano, T., Hirayama, D., Wagatsuma, K., Yamakawa, T., Yokoyama, Y., and Nakase, H. (2020). Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093062"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1158\/1078-0432.CCR-03-0192","article-title":"Cyclooxygenase-2 Activation Mediates the Proangiogenic Effect of Nitric Oxide in Colorectal Cancer","volume":"10","author":"Cianchi","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1365-2796.2008.01953.x","article-title":"NF-\u03baB in inflammatory bowel disease","volume":"263","author":"Atreya","year":"2008","journal-title":"J. Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.bcp.2015.07.039","article-title":"Dipotassium glycyrrhizate via HMGB1 or AMPK signaling suppresses oxidative stress during intestinal inflammation","volume":"97","author":"Vitali","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1158\/1940-6207.CAPR-08-0028","article-title":"Increased Susceptibility of Nrf2 Knockout Mice to Colitis-Associated Colorectal Cancer","volume":"1","author":"Khor","year":"2008","journal-title":"Cancer Prev. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6017","DOI":"10.7314\/APJCP.2012.13.12.6017","article-title":"Resveratrol affects protein kinase C activity and promotes apoptosis in human colon carcinoma cells","volume":"13","author":"Fang","year":"2012","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"18748","DOI":"10.18632\/oncotarget.4349","article-title":"Targeting cancer by binding iron: Dissecting cellular signaling pathways","volume":"6","author":"Lui","year":"2015","journal-title":"Oncotarget"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1743-7075-11-21","article-title":"Systemic and tumor level iron regulation in men with colorectal cancer: A case control study","volume":"11","author":"Pusatcioglu","year":"2014","journal-title":"Nutr. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s10534-009-9231-6","article-title":"Elemental fingerprinting of tumorous and adjacent non-tumorous tissues from patients with colorectal cancer using ICP-MS, ICP-OES and chemometric analysis","volume":"22","author":"Lavilla","year":"2009","journal-title":"BioMetals"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9","DOI":"10.5625\/lar.2011.27.1.9","article-title":"Effects of selenium on colon carcinogenesis induced by azoxymethane and dextran sodium sulfate in mouse model with high-iron diet","volume":"27","author":"Kim","year":"2011","journal-title":"Lab. Anim. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"15382","DOI":"10.1074\/jbc.273.25.15382","article-title":"Role of ferritin in the control of the labile iron pool in murine erythroleukemia cells","volume":"273","author":"Picard","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1158\/1078-0432.CCR-04-0631","article-title":"Ferritin Contributes to Melanoma Progression by Modulating Cell Growth and Sensitivity to Oxidative Stress","volume":"11","author":"Baldi","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s10549-010-0849-4","article-title":"Role of ferritin alterations in human breast cancer cells","volume":"126","author":"Shpyleva","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1111\/cas.13234","article-title":"BRAF mutations are associated with increased iron regulatory protein-2 expression in colorectal tumorigenesis","volume":"108","author":"Horniblow","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1136\/gut.2006.094060","article-title":"Modulation of iron transport proteins in human colorectal carcinogenesis","volume":"55","author":"Brookes","year":"2006","journal-title":"Gut"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.canlet.2005.07.001","article-title":"Altered iron metabolism, transferrin receptor 1 and ferritin in patients with colon cancer","volume":"238","author":"Prutki","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1002\/iub.1621","article-title":"Ferritin, cellular iron storage and regulation","volume":"69","author":"Arosio","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Sim\u00e3o, M., Camacho, A., Ostertag, A., Cohen-Solal, M., Pinto, I.J., Porto, G., Hang Korng, E., and Cancela, M.L. (2018). Iron-enriched diet contributes to early onset of osteoporotic phenotype in a mouse model of hereditary hemochromatosis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207441"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s10534-018-0123-5","article-title":"Iron chelation inhibits cancer cell growth and modulates global histone methylation status in colorectal cancer","volume":"31","author":"Cao","year":"2018","journal-title":"BioMetals"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1002\/hep.24178","article-title":"Evidence for distinct pathways of hepcidin regulation by acute and chronic iron loading in mice","volume":"53","author":"Ramos","year":"2011","journal-title":"Hepatology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1182\/blood-2003-04-1250","article-title":"Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages","volume":"102","author":"Knutson","year":"2003","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3945\/jn.108.094052","article-title":"Iron Loading Increases Ferroportin Heterogeneous Nuclear RNA and mRNA Levels in Murine J774 Macrophages","volume":"139","author":"Aydemir","year":"2009","journal-title":"J. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"G554","DOI":"10.1152\/ajpgi.00486.2010","article-title":"Iron loading and oxidative stress in the Atm\u2212\/\u2212 mouse liver","volume":"300","author":"McDonald","year":"2011","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"F1050","DOI":"10.1152\/ajprenal.00064.2003","article-title":"Altered dietary iron intake is a strong modulator of renal DMT1 expression","volume":"285","author":"Wareing","year":"2003","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.cmet.2012.09.001","article-title":"Divalent Metal Transporter 1 Regulates Iron-Mediated ROS and Pancreatic \u03b2 Cell Fate in Response to Cytokines","volume":"16","author":"Hansen","year":"2012","journal-title":"Cell Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1530\/JME-17-0262","article-title":"Glucolipotoxic conditions induce \u03b2-cell iron import, cytosolic ROS formation and apoptosis","volume":"61","author":"Hansen","year":"2018","journal-title":"J. Mol. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1042\/BST0370605","article-title":"PCNA on the crossroad of cancer","volume":"37","author":"Stoimenov","year":"2009","journal-title":"Biochem. Soc. Trans."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1038\/onc.2009.512","article-title":"Myc proteins as therapeutic targets","volume":"29","author":"Gustafson","year":"2010","journal-title":"Oncogene"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1111\/j.1349-7006.2007.00449.x","article-title":"Functions of cyclin D1 as an oncogene and regulation of cyclin D1 expression","volume":"98","author":"Tashiro","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"923","DOI":"10.3892\/ijmm.2015.2298","article-title":"In-depth analysis of the critical genes and pathways in colorectal cancer","volume":"36","author":"Liu","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"126582","DOI":"10.1016\/j.jtemb.2020.126582","article-title":"Iron: Key player in cancer and cell cycle?","volume":"62","author":"Khan","year":"2020","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1046\/j.1523-1747.2000.00119.x","article-title":"Iron chelators inhibit the growth and induce the apoptosis of Kaposi\u2019s sarcoma cells and of their putative endothelial precursors","volume":"115","author":"Simonart","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1093\/humrep\/del261","article-title":"Iron overload enhances epithelial cell proliferation in endometriotic lesions induced in a murine model","volume":"21","author":"Vaesen","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.trsl.2006.03.002","article-title":"Chronic iron overload stimulates hepatocyte proliferation and cyclin D1 expression in rodent liver","volume":"148","author":"Brown","year":"2006","journal-title":"Transl. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2017.05.023","article-title":"ROS signalling in the biology of cancer","volume":"80","author":"Moloney","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.cmet.2020.10.011","article-title":"The Metabolic Underpinnings of Ferroptosis","volume":"32","author":"Zheng","year":"2020","journal-title":"Cell Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"106094","DOI":"10.1016\/j.biocel.2021.106094","article-title":"Cancer: The role of iron and ferroptosis","volume":"141","author":"Rishi","year":"2021","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"104919","DOI":"10.1016\/j.phrs.2020.104919","article-title":"The Application of Ferroptosis in Diseases","volume":"159","author":"Qiu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1007\/s00204-012-0906-3","article-title":"Oxidative stress in apoptosis and cancer: An update","volume":"86","author":"Segura","year":"2012","journal-title":"Arch. Toxicol."},{"key":"ref_91","first-page":"21","article-title":"NF-\u03baB pathway in colitis-associated cancers","volume":"2","author":"Viennois","year":"2013","journal-title":"Transl. Gastrointest. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.cell.2004.07.013","article-title":"IKK\u03b2 Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer","volume":"118","author":"Greten","year":"2004","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/jgh.12435","article-title":"Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer","volume":"29","author":"Koh","year":"2014","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.phrs.2019.04.010","article-title":"Saponins regulate intestinal inflammation in colon cancer and IBD","volume":"144","author":"Dong","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"G9","DOI":"10.1152\/ajpgi.00267.2010","article-title":"Fluoxetine inhibits NF-\u03baB signaling in intestinal epithelial cells and ameliorates experimental colitis and colitis-associated colon cancer in mice","volume":"301","author":"Koh","year":"2011","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ccr.2009.01.001","article-title":"IL-6 and Stat3 Are Required for Survival of Intestinal Epithelial Cells and Development of Colitis-Associated Cancer","volume":"15","author":"Grivennikov","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_97","first-page":"560","article-title":"Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis","volume":"118","author":"Popivanova","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.acthis.2012.02.004","article-title":"The expression of iNOS and nitrotyrosine in colitis and colon cancer in humans","volume":"114","author":"Gochman","year":"2012","journal-title":"Acta Histochem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/onc.2009.421","article-title":"The role of COX-2 in intestinal inflammation and colorectal cancer","volume":"29","author":"Wang","year":"2010","journal-title":"Oncogene"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"376","DOI":"10.7326\/0003-4819-146-5-200703060-00010","article-title":"Nonsteroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Inhibitors for Primary Prevention of Colorectal Cancer: A Systematic Review Prepared for the U.S. Preventive Services Task Force","volume":"146","author":"Alaa","year":"2007","journal-title":"Ann. Intern. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s12307-009-0030-y","article-title":"The NF-\u03baB\/AKT-dependent Induction of Wnt Signaling in Colon Cancer Cells by Macrophages and IL-1\u03b2","volume":"2","author":"Kaler","year":"2009","journal-title":"Cancer Microenviron."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1097\/MIB.0000000000001089","article-title":"Iron Supplements Modulate Colon Microbiota Composition and Potentiate the Protective Effects of Probiotics in Dextran Sodium Sulfate-induced Colitis","volume":"23","author":"Constante","year":"2017","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5276130","DOI":"10.1155\/2016\/5276130","article-title":"Role of antioxidants and natural products in inflammation","volume":"2016","author":"Arulselvan","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"101760","DOI":"10.1016\/j.redox.2020.101760","article-title":"SOD1 suppresses pro-inflammatory immune responses by protecting against oxidative stress in colitis","volume":"37","author":"Hwang","year":"2020","journal-title":"Redox Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1073\/pnas.91.5.1672","article-title":"Distinct effects of thioredoxin and antioxidants on the activation of transcription factors NF-kappa B and AP-1","volume":"91","author":"Schenk","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"G848","DOI":"10.1152\/ajpgi.2001.281.3.G848","article-title":"Mice with combined disruption of Gpx1 andGpx2 genes have colitis","volume":"281","author":"Esworthy","year":"2001","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1093\/toxsci\/kfs193","article-title":"Elevated Hepatic Iron Activates NF-E2\u2013Related Factor 2\u2013Regulated Pathway in a Dietary Iron Overload Mouse Model","volume":"129","author":"Moon","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Li, C., Deng, X., Xie, X., Liu, Y., Friedmann Angeli, J.P., and Lai, L. (2018). Activation of Glutathione Peroxidase 4 as a Novel Anti-inflammatory Strategy. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01120"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6730","DOI":"10.4049\/jimmunol.181.10.6730","article-title":"Lipopolysaccharide-Induced Expression of NAD(P)H:Quinone Oxidoreductase 1 and Heme Oxygenase-1 Protects against Excessive Inflammatory Responses in Human Monocytes","volume":"181","author":"Rushworth","year":"2008","journal-title":"J. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1158\/1078-0432.CCR-09-2283","article-title":"New Strategies in Colorectal Cancer: Biomarkers of Response to Epidermal Growth Factor Receptor Monoclonal Antibodies and Potential Therapeutic Targets in Phosphoinositide 3-Kinase and Mitogen-Activated Protein Kinase Pathways","volume":"16","author":"Dasari","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1053\/j.gastro.2011.05.010","article-title":"Targeting PI3K Signaling as a Therapeutic Approach for Colorectal Cancer","volume":"141","author":"Zhang","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ygyno.2021.07.008","article-title":"The effectiveness of monotherapy with PI3K\/AKT\/mTOR pathway inhibitors in ovarian cancer: A meta-analysis","volume":"163","author":"Uittenboogaard","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2217\/lmt.13.72","article-title":"Targeting the PI3K\/AKT\/mTOR pathway: Potential for lung cancer treatment","volume":"3","author":"Cheng","year":"2014","journal-title":"Lung Cancer Manag."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Agarwal, E., Chaudhuri, A., Leiphrakpam, P.D., Haferbier, K.L., Brattain, M.G., and Chowdhury, S. (2014). Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-145"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41598-017-00057-3","article-title":"Genomic variants in mouse model induced by azoxymethane and dextran sodium sulfate improperly mimic human colorectal cancer","volume":"7","author":"Pan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S1535-6108(03)00248-4","article-title":"Targeting the PI3K-Akt pathway in human cancer: Rationale and promise","volume":"4","author":"Luo","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1158\/0008-5472.CAN-18-2738","article-title":"AKT as a Therapeutic Target for Cancer","volume":"79","author":"Song","year":"2019","journal-title":"Cancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12943-019-0954-x","article-title":"Targeting PI3K in cancer: Mechanisms and advances in clinical trials","volume":"18","author":"Yang","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K\u2013AKT network at the interface of oncogenic signalling and cancer metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1007\/s10620-012-2237-x","article-title":"Deguelin, an Akt inhibitor, down-regulates NF-\u03baB signaling and induces apoptosis in colon cancer cells and inhibits tumor growth in mice","volume":"57","author":"Kang","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.cellsig.2013.03.025","article-title":"Cell survival and metastasis regulation by Akt signaling in colorectal cancer","volume":"25","author":"Agarwal","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1111\/odi.12662","article-title":"Iron overload induces apoptosis of murine preosteoblast cells via ROS and inhibition of AKT pathway","volume":"23","author":"Ke","year":"2017","journal-title":"Oral Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3389\/fphar.2019.00163","article-title":"Icariin Protects Bone Marrow Mesenchymal Stem Cells Against Iron Overload Induced Dysfunction Through Mitochondrial Fusion and Fission, PI3K\/AKT\/mTOR and MAPK Pathways","volume":"10","author":"Yao","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e22729","DOI":"10.1002\/jbt.22729","article-title":"Modulating NF-\u03baB, MAPK, and PI3K\/AKT signaling by ergothioneine attenuates iron overload-induced hepatocellular injury in rats","volume":"35","author":"Salama","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"109230","DOI":"10.1016\/j.cbi.2020.109230","article-title":"Taxifolin ameliorates iron overload-induced hepatocellular injury: Modulating PI3K\/AKT and p38 MAPK signaling, inflammatory response, and hepatocellular regeneration","volume":"330","author":"Salama","year":"2020","journal-title":"Chem.-Biol. Interact."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/bjc.2012.582","article-title":"Dp44mT targets the AKT, TGF-\u03b2 and ERK pathways via the metastasis suppressor NDRG1 in normal prostate epithelial cells and prostate cancer cells","volume":"108","author":"Dixon","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1089\/ars.2011.4273","article-title":"The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4 and inhibits the PI3K and Ras signaling pathways","volume":"18","author":"Kovacevic","year":"2013","journal-title":"Antioxid. Redox Signal."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/10\/2033\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:09:49Z","timestamp":1760137789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/10\/2033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":127,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["nu14102033"],"URL":"https:\/\/doi.org\/10.3390\/nu14102033","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,12]]}}}