Biological and Immunological Aspects of Iron Deficiency Anemia in Cancer Development: A Narrative Review

References

• WHO C: Worldwide prevalence of anaemia 1993–2005. WHO global database on anaemia 2008.
   Google Scholar
• McLean E, Cogswell M, Egli I, Wojdyla D, and de Benoist B: Worldwide prevalence of anaemia, WHO vitamin and mineral nutrition information system, 1993–2005. Public Health Nutr 12, 444–454, 2009. doi:10.1017/s1368980008002401.
   PubMed Web of Science ®Google Scholar
• Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, et al.: A systematic analysis of global anemia burden from 1990 to 2010. Blood 123, 615–624, 2014.
   PubMed Web of Science ®Google Scholar
• Organization WH: Iron deficiency anaemia: assessment, prevention and control: a guide for programme managers. 2001.
   Google Scholar
• Camaschella C: Iron-deficiency anemia. N Engl J Med 372, 1832–1843, 2015. doi:10.1056/NEJMra1401038.
   PubMed Web of Science ®Google Scholar
• Lopez A, Cacoub P, Macdougall IC, and Peyrin-Biroulet L: Iron deficiency anaemia. Lancet 2015. doi:10.1016/s0140-6736(15)60865-0.
   PubMed Web of Science ®Google Scholar
• Balarajan Y, Ramakrishnan U, Özaltin E, Shankar AH, and Subramanian S: Anaemia in low-income and middle-income countries. The Lancet 378, 2123–2135, 2012.
   Web of Science ®Google Scholar
• Chmielewska A, Dziechciarz P, Gieruszczak-Bialek D, Horvath A, Piescik-Lech M, et al.: Effects of prenatal and/or postnatal supplementation with iron, PUFA or folic acid on neurodevelopment: update. Br J Nutr 1–6, 2016. doi:10.1017/s0007114514004243.
   PubMedGoogle Scholar
• Christian P: Micronutrients, birth weight, and survival. Annu Rev Nutr 30, 83–104, 2010. doi:10.1146/annurev.nutr.012809.104813.
   PubMed Web of Science ®Google Scholar
• Beard JL and Connor JR: Iron status and neural functioning. Annu Rev Nutr 23, 41–58, 2003. doi:10.1146/annurev.nutr.23.020102.075739.
   PubMed Web of Science ®Google Scholar
• McClung JP and Murray-Kolb LE: Iron nutrition and premenopausal women: effects of poor iron status on physical and neuropsychological performance. Annu Rev Nutr 33, 271–288, 2013. doi:10.1146/annurev-nutr-071812-161205.
   PubMed Web of Science ®Google Scholar
• Enjuanes C, Klip IT, Bruguera J, Cladellas M, Ponikowski P, et al.: Iron deficiency and health-related quality of life in chronic heart failure: results from a multicenter European study. Int J Cardiol 174, 268–275, 2014.
   PubMed Web of Science ®Google Scholar
• Gilreath JA, Stenehjem DD, and Rodgers GM: Diagnosis and treatment of cancer‐related anemia. Am J Hematol 89, 203–212, 2014.
   PubMed Web of Science ®Google Scholar
• Fishbane S, Pollack S, Feldman HI, and Joffe MM: Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988–2004. Clin J Am Soc Nephrol 4, 57–61, 2009.
   PubMed Web of Science ®Google Scholar
• Bager P, Befrits R, Wikman O, Lindgren S, Moum B, et al.: The prevalence of anemia and iron deficiency in IBD outpatients in Scandinavia. Scand J Gastroenterol 46, 304–309, 2011.
   PubMed Web of Science ®Google Scholar
• Safaralizadeh R, Kardar G, Pourpak Z, Moin M, Zare A, et al.: Serum concentration of selenium in healthy individuals living in Tehran. Nutr J 4, 1–4, 2005.
   PubMed Web of Science ®Google Scholar
• Safaralizadeh R, Nourizadeh M, Zare A, Kardar GA, and Pourpak Z: Influence of selenium on mast cell mediator release. Biol Trace Elem Res 154, 299–303, 2013.
   PubMed Web of Science ®Google Scholar
• Zare A, Saremi A, Hajhashemi M, Kardar GA, Moazzeni SM, et al.: Correlation between serum zinc levels and successful immunotherapy in recurrent spontaneous abortion patients. J Hum Reprod Sci 6, 147–51, 2013. doi:10.4103/0974-1208.117170.
   PubMedGoogle Scholar
• Muñoz C, Rios E, Olivos J, Brunser O, and Olivares M: Iron, copper and immunocompetence. Br J Nutr 98, S24–S28, 2007.
   PubMed Web of Science ®Google Scholar
• Liu L and Huang M: Essential role of the iron-sulfur cluster binding domain of the primase regulatory subunit Pri2 in DNA replication initiation. Protein Cell 6, 194–210, 2015. doi:10.1007/s13238-015-0134-8.
   PubMed Web of Science ®Google Scholar
• Dostal A, Lacroix C, Pham VT, Zimmermann MB, Del'homme C, et al.: Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats. Br J Nutr 111, 2135–2145, 2014. doi:10.1017/s000711451400021x.
   PubMed Web of Science ®Google Scholar
• Bohnsack BL and Hirschi KK: Nutrient regulation of cell cycle progression. Annu Rev Nutr 24, 433–453, 2004.
   PubMed Web of Science ®Google Scholar
• Hung N, Shen C-C, Hu Y-W, Hu L-Y, Yeh C-M, et al.: Risk of cancer in patients with iron deficiency anemia: a nationwide population-based study. PloS one 10, e0119647, 2015.
   PubMed Web of Science ®Google Scholar
• Ahluwalia N, Sun J, Krause D, Mastro A, and Handte G: Immune function is impaired in iron-deficient, homebound, older women. Am J Clin Nutr 79, 516–521, 2004.
   PubMed Web of Science ®Google Scholar
• Kumar V and Choudhry VP: Iron deficiency and infection. Indian J Pediatr 77, 789–93, 2010. doi:10.1007/s12098-010-0120-3.
   PubMed Web of Science ®Google Scholar
• Nakama H, Zhang B, Fattah AA, and Zhang X: Colorectal cancer in iron deficiency anemia with a positive result on immunochemical fecal occult blood. Int J Colorectal dis 15, 271–274, 2000.
   PubMed Web of Science ®Google Scholar
• Richie JP, Kleinman W, Marina P, Abraham P, Wynder EL, et al.: Blood iron, glutathione, and micronutrient levels and the risk of oral cancer. Nutr Cancer 60, 474–482, 2008.
   PubMed Web of Science ®Google Scholar
• Ioannou GN, Rockey DC, Bryson CL, and Weiss NS: Iron deficiency and gastrointestinal malignancy: a population-based cohort study. Am J Med 113, 276–280, 2002.
   PubMed Web of Science ®Google Scholar
• James MW, Chen C-M, Goddard WP, Scott BB, and Goddard AF: Risk factors for gastrointestinal malignancy in patients with iron-deficiency anaemia. Eur J Gastroenterol Hepatol 17, 1197–1203, 2005.
   PubMed Web of Science ®Google Scholar
• Kurtoglu E, Ugur A, Baltaci AK, and Undar L: Effect of iron supplementation on oxidative stress and antioxidant status in iron-deficiency anemia. Biol Trace Elem Res 96, 117–123, 2003.
   PubMed Web of Science ®Google Scholar
• Akca H, Polat A, and Koca C: Determination of total oxidative stress and total antioxidant capacity before and after the treatment of iron-deficiency anemia. J Clin Lab Anal 27, 227–230, 2013. doi:10.1002/jcla.21589.
   PubMed Web of Science ®Google Scholar
• Bagheri F, Khori V, Alizadeh AM, Khalighfard S, Khodayari S, et al.: Reactive oxygen species-mediated cardiac-reperfusion injury: mechanisms and therapies. Life Sci 2016. doi:10.1016/j.lfs.2016.09.013.
   Web of Science ®Google Scholar
• Harrison IP and Selemidis S: Understanding the biology of reactive oxygen species and their link to cancer: NADPH oxidases as novel pharmacological targets. Clin Exp Pharmacol Physiol 41, 533–542, 2014. doi:10.1111/1440-1681.12238.
   PubMed Web of Science ®Google Scholar
• Chen X, Song M, Zhang B, and Zhang Y: Reactive oxygen species regulate T cell immune response in the tumor microenvironment. Oxid Med Cell Longev 2016, 1580967, 2016. doi:10.1155/2016/1580967.
   PubMed Web of Science ®Google Scholar
• Sundaram RC, Selvaraj N, Vijayan G, Bobby Z, Hamide A, et al.: Increased plasma malondialdehyde and fructosamine in iron deficiency anemia: effect of treatment. Biomed Pharmacother 61, 682–685, 2007. doi:10.1016/j.biopha.2007.06.013.
   PubMed Web of Science ®Google Scholar
• Toblli J, Cao G, Oliveri L, and Angerosa M: Effects of iron deficiency anemia and its treatment with iron polymaltose complex in pregnant rats, their fetuses and placentas: oxidative stress markers and pregnancy outcome. Placenta 33, 81–87, 2012.
   PubMed Web of Science ®Google Scholar
• Inoue H, Kobayashi K, Ndong M, Yamamoto Y, Katsumata S, et al.: Activation of Nrf2/Keap1 signaling and autophagy induction against oxidative stress in heart in iron deficiency. Biosci Biotechnol Biochem 79, 1366–1368, 2015. doi:10.1080/09168451.2015.1018125.
   PubMed Web of Science ®Google Scholar
• El-Shimi MS, El-Farrash RA, Ismail EA, El-Safty A, Nada AS, et al.: Renal functional and structural integrity in infants with iron deficiency anemia: relation to oxidative stress and response to iron therapy. Pediatric Nephrology 30, 1835–1842, 2015.
   PubMed Web of Science ®Google Scholar
• Yoo JH, Maeng HY, Sun YK, Kim YA, Park DW, et al.: Oxidative status in iron-deficiency anemia. J Clin Lab Anal 23, 319–323, 2009. doi:10.1002/jcla.20335.
   PubMed Web of Science ®Google Scholar
• Wu Q and Ni X: ROS-mediated DNA methylation pattern alterations in carcinogenesis. Curr Drug Targets 16, 13–19, 2015.
   PubMed Web of Science ®Google Scholar
• Atamna H: Heme, iron, and the mitochondrial decay of ageing. Ageing Res Rev 3, 303–318, 2004.
   PubMed Web of Science ®Google Scholar
• Lill R, Dutkiewicz R, Freibert SA, Heidenreich T, Mascarenhas J, et al.: The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron-sulfur proteins. Eur J Cell Biol 94, 280–291, 2015. doi:10.1016/j.ejcb.2015.05.002.
   PubMed Web of Science ®Google Scholar
• Kaniak-Golik A and Skoneczna A: Mitochondria-nucleus network for genome stability. Free Radic Biol Med 82, 73–104, 2015. doi:10.1016/j.freeradbiomed.2015.01.013.
   PubMed Web of Science ®Google Scholar
• Hirst J and Roessler MM: Energy conversion, redox catalysis and generation of reactive oxygen species by respiratory complex I. Biochim Biophys Acta 1857, 872–883, 2016. doi:10.1016/j.bbabio.2015.12.009.
   PubMed Web of Science ®Google Scholar
• Walter PB, Knutson MD, Paler-Martinez A, Lee S, Xu Y, et al.: Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Nat Acad Sci 99, 2264–2269, 2002.
   PubMed Web of Science ®Google Scholar
• Atamna H, Killilea DW, Killilea AN, and Ames BN: Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging. Proc Natl Acad Sci U S A 99, 14807–14812, 2002. doi:10.1073/pnas.192585799.
   PubMed Web of Science ®Google Scholar
• Wallace DC: A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. The FASEB J 20, A1474, 2006.
   Web of Science ®Google Scholar
• Mettert EL and Kiley PJ: Fe-S proteins that regulate gene expression. Biochim Biophys Acta 1853, 1284–1293, 2015. doi:10.1016/j.bbamcr.2014.11.018.
   PubMed Web of Science ®Google Scholar
• Kimura S and Suzuki T: Iron-sulfur proteins responsible for RNA modifications. Biochim Biophys Acta 1853, 1272–1283, 2015. doi:10.1016/j.bbamcr.2014.12.010.
   PubMed Web of Science ®Google Scholar
• Paul VD and Lill R: Biogenesis of cytosolic and nuclear iron-sulfur proteins and their role in genome stability. Biochim Biophys Acta 1853, 1528–1539, 2015. doi:10.1016/j.bbamcr.2014.12.018.
   PubMed Web of Science ®Google Scholar
• Zhang C: Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control. Protein Cell 5, 750–760, 2014.
   PubMed Web of Science ®Google Scholar
• Prá D, Franke SIR, Henriques JAP, and Fenech M: Iron and genome stability: an update. Mutat Res/Fundam Mol Mech Mutagen 733, 92–99, 2012.
   PubMed Web of Science ®Google Scholar
• White MF: Structure, function and evolution of the XPD family of iron-sulfur-containing 5′→ 3′ DNA helicases. Biochem Soc Trans 37, 547–551, 2009.
   PubMed Web of Science ®Google Scholar
• Rouault TA and Tong WH: Iron-sulfur cluster biogenesis and human disease. Trends Genet 24, 398–407, 2008. doi:10.1016/j.tig.2008.05.008.
   PubMed Web of Science ®Google Scholar
• Ye H and Rouault TA: Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. Biochemistry 49, 4945–4956, 2010. doi:10.1021/bi1004798.
   PubMed Web of Science ®Google Scholar
• Boyd ES, Thomas KM, Dai Y, Boyd JM, and Outten FW: Interplay between oxygen and Fe-S cluster biogenesis: insights from the Suf pathway. Biochemistry 53, 5834–5847, 2014. doi:10.1021/bi500488r.
   PubMed Web of Science ®Google Scholar
• Macheret M and Halazonetis TD: DNA replication stress as a hallmark of cancer. Annu Rev Pathol 10, 425–448, 2015. doi:10.1146/annurev-pathol-012414-040424.
   PubMed Web of Science ®Google Scholar
• Aslan M, Horoz M, Kocyigit A, Ozgonül S, Celik H, et al.: Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia. Mutat Res/Fundam Mol Mech Mutagen 601, 144–149, 2006.
   PubMed Web of Science ®Google Scholar
• Khabour OF, Soudah OA, and Aaysh MH: Genotoxicity assessment in iron deficiency anemia patients using sister chromatid exchanges and chromosomal aberrations assays. Mutat Res 750, 72–6, 2013. doi:10.1016/j.mrgentox.2012.09.006.
   PubMed Web of Science ®Google Scholar
• Prá D, Bortoluzzi A, Müller LL, Hermes L, Horta JA, et al.: Iron intake, red cell indicators of iron status, and DNA damage in young subjects. Nutrition 27, 293–297, 2011.
   PubMed Web of Science ®Google Scholar
• Díaz-Castro J, Alférez MJ, López-Aliaga I, Nestares T, Granados S, et al.: Influence of nutritional iron deficiency anemia on DNA stability and lipid peroxidation in rats. Nutrition 24, 1167–1173, 2008.
   PubMed Web of Science ®Google Scholar
• Koury MJ and Ponka P: New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr 24, 105–131, 2004.
   PubMed Web of Science ®Google Scholar
• Remacha AF, Wright I, Fernandez-Jimenez MC, Toxqui L, Blanco-Rojo R, et al.: Vitamin B12 and folate levels increase during treatment of iron deficiency anaemia in young adult woman. Int J Lab Hematol 37, 641–648, 2015. doi:10.1111/ijlh.12378.
   PubMed Web of Science ®Google Scholar
• Wang T-C, Song Y-S, Wang H, Zhang J, Yu S-F, et al.: Oxidative DNA damage and global DNA hypomethylation are related to folate deficiency in chromate manufacturing workers. J Hazard Mater 213, 440–446, 2012.
   PubMed Web of Science ®Google Scholar
• Geng Y, Gao R, Chen X, Liu X, Liao X, et al.: Folate deficiency impairs decidualization and alters methylation patterns of the genome in mice. Mol Hum Reprod gav045, 2015.
   Web of Science ®Google Scholar
• Duthie SJ, Narayanan S, Blum S, Pirie L, and Brand GM: Folate deficiency in vitro induces uracil misincorporation and DNA hypomethylation and inhibits DNA excision repair in immortalized normal human colon epithelial cells. Nutr Cancer 37, 245–251, 2000. doi:10.1207/s15327914nc372_18.
   PubMed Web of Science ®Google Scholar
• Iwakawa HO and Tomari Y: The functions of MicroRNAs: mRNA decay and translational repression. Trends Cell Biol 25, 651–665, 2015. doi:10.1016/j.tcb.2015.07.011.
   PubMed Web of Science ®Google Scholar
• Mansoori B, Mohammadi A, Shirjang S, and Baradaran B: Micro-RNAs: The new potential biomarkers in cancer diagnosis, prognosis and cancer therapy. Cell Mol Biol (Noisy-le-grand) 61, 1–10, 2015.
   PubMed Web of Science ®Google Scholar
• Pauley KM and Chan EK: MicroRNAs and their emerging roles in immunology. Ann N Y Acad Sci 1143, 226–239, 2008. doi:10.1196/annals.1443.009.
   PubMed Web of Science ®Google Scholar
• O'Connell RM, Rao DS, and Baltimore D: MicroRNA regulation of inflammatory responses. Annu Rev Immunol 30, 295–312, 2012.
   PubMed Web of Science ®Google Scholar
• Wang J, Yu F, Jia X, Iwanowycz S, Wang Y, et al.: MicroRNA‐155 deficiency enhances the recruitment and functions of myeloid‐derived suppressor cells in tumor microenvironment and promotes solid tumor growth. Int J Cancer 136, E602–E613, 2015.
   PubMed Web of Science ®Google Scholar
• Davis M and Clarke S: Influence of microRNA on the maintenance of human iron metabolism. Nutrients 5, 2611–2628, 2013.
   PubMed Web of Science ®Google Scholar
• Weitz SH, Gong M, Barr I, Weiss S, and Guo F: Processing of microRNA primary transcripts requires heme in mammalian cells. Proc Natl Acad Sci U S A 111, 1861–1866, 2014. doi:10.1073/pnas.1309915111.
   PubMed Web of Science ®Google Scholar
• Li Y, Lin L, Li Z, Ye X, Xiong K, et al.: Iron homeostasis regulates the activity of the microRNA pathway through poly(C)-binding protein 2. Cell Metab 15, 895–904, 2012. doi:10.1016/j.cmet.2012.04.021.
   PubMed Web of Science ®Google Scholar
• Nallamshetty S, Chan SY, and Loscalzo J: Hypoxia: A master regulator of microRNA biogenesis and activity. Free Radical Biol Med 64, 20–30, 2013. doi:https://doi.org/10.1016/j.freeradbiomed.2013.05.022.
   PubMed Web of Science ®Google Scholar
• Bao B, S Azmi A, Li Y, Ahmad A, Ali S, et al.: Targeting CSCs in tumor microenvironment: the potential role of ROS-associated miRNAs in tumor aggressiveness. Curr Stem Cell Res Therapy 9, 22–35, 2014.
   PubMed Web of Science ®Google Scholar
• Devlin C, Greco S, Martelli F, and Ivan M: miR-210: more than a silent player in hypoxia. IUBMB Life 63, 94–100, 2011. doi:10.1002/iub.427.
   PubMed Web of Science ®Google Scholar
• Crosby ME, Kulshreshtha R, Ivan M, and Glazer PM: MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res 69, 1221–1229, 2009.
   PubMed Web of Science ®Google Scholar
• Akao Y, Nakagawa Y, and Naoe T: let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull 29, 903–906, 2006.
   PubMed Web of Science ®Google Scholar
• Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, et al.: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64, 3753–3756, 2004. doi:10.1158/0008-5472.can-04-0637.
   PubMed Web of Science ®Google Scholar
• Yang Q, Jie Z, Cao H, Greenlee AR, Yang C, et al.: Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C. Carcinogenesis 32, 713–722, 2011. doi:10.1093/carcin/bgr035.
   PubMed Web of Science ®Google Scholar
• Chang CJ, Hsu CC, Chang CH, Tsai LL, Chang YC, et al.: Let-7d functions as novel regulator of epithelial-mesenchymal transition and chemoresistant property in oral cancer. Oncol Rep 26, 1003–1010, 2011. doi:10.3892/or.2011.1360.
   PubMed Web of Science ®Google Scholar
• Wang Z, Liu Y, Han N, Chen X, Yu W, et al.: Profiles of oxidative stress-related microRNA and mRNA expression in auditory cells. Brain Res 1346, 14–25, 2010. doi:10.1016/j.brainres.2010.05.059.
   PubMed Web of Science ®Google Scholar
• Silván U, Díez-Torre A, Bonilla Z, Moreno P, Díaz-Núñez M, et al.: Vasculogenesis and angiogenesis in nonseminomatous testicular germ cell tumors. Urol Oncol: Semin Orig Investig 33, 268.e17–268.e28, 2015. doi:https://doi.org/10.1016/j.urolonc.2015.01.005.
   PubMed Web of Science ®Google Scholar
• Lee SH, Jeong D, Han YS, and Baek MJ: Pivotal role of vascular endothelial growth factor pathway in tumor angiogenesis. Ann Surg Treat Res 89, 1–8, 2015. doi:10.4174/astr.2015.89.1.1.
   PubMed Web of Science ®Google Scholar
• Esser JS, Rahner S, Deckler M, Bode C, Patterson C, et al.: Fibroblast growth factor signaling pathway in endothelial cells is activated by BMPER to promote angiogenesis. Arterioscler Thromb Vasc Biol 35, 358–367, 2015. doi:10.1161/atvbaha.114.304345.
   PubMed Web of Science ®Google Scholar
• Bornstein P: Thrombospondins function as regulators of angiogenesis. J Cell Commun Signal 3, 189–200, 2009. doi:10.1007/s12079-009-0060-8.
   PubMed Web of Science ®Google Scholar
• Jian J, Yang Q, Dai J, Eckard J, Axelrod D, et al.: Effects of iron deficiency and iron overload on angiogenesis and oxidative stress—a potential dual role for iron in breast cancer. Free Radical Biol Med 50, 841–847, 2011.
   PubMed Web of Science ®Google Scholar
• Fraga A, Ribeiro R, Príncipe P, Lopes C, and Medeiros R: Hypoxia and prostate cancer aggressiveness: a tale with many endings. Clinical Genitourinary Cancer 13, 295–301, 2015. doi:https://doi.org/10.1016/j.clgc.2015.03.006.
   PubMed Web of Science ®Google Scholar
• Huang X: Does iron have a role in breast cancer? The Lancet Oncol 9, 803–807, 2008.
   PubMed Web of Science ®Google Scholar
• Xue X, Taylor M, Anderson E, Hao C, Qu A, et al.: Hypoxia-inducible factor-2α activation promotes colorectal cancer progression by dysregulating iron homeostasis. Cancer Res 72, 2285–2293, 2012.
   PubMed Web of Science ®Google Scholar
• Jian J, Yang Q, Shao Y, Axelrod D, Smith J, et al.: A link between premenopausal iron deficiency and breast cancer malignancy. BMC Cancer 13, 307, 2013.
   PubMed Web of Science ®Google Scholar
• Cichon MA and Radisky DC: ROS-induced epithelial-mesenchymal transition in mammary epithelial cells is mediated by NF-kB-dependent activation of Snail. Oncotarget 5, 2827–2838, 2014. doi:10.18632/oncotarget.1940.
   PubMedGoogle Scholar
• Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, et al.: Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436, 123–127, 2005. doi:10.1038/nature03688.
   PubMed Web of Science ®Google Scholar
• Elmore S: Apoptosis: a review of programmed cell death. Toxicol Pathol 35, 495–516, 2007.
   PubMed Web of Science ®Google Scholar
• Garrido C, Galluzzi L, Brunet M, Puig P, Didelot C, et al.: Mechanisms of cytochrome c release from mitochondria. Cell Death Differ 13, 1423–1433, 2006.
   PubMed Web of Science ®Google Scholar
• Hill MM, Adrain C, Duriez PJ, Creagh EM, and Martin SJ: Analysis of the composition, assembly kinetics and activity of native Apaf‐1 apoptosomes. EMBO J 23, 2134–2145, 2004.
   PubMed Web of Science ®Google Scholar
• Fulda S and Debatin K: Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25, 4798–4811, 2006.
   PubMed Web of Science ®Google Scholar
• Cain K, Bratton SB, and Cohen GM: The Apaf-1 apoptosome: a large caspase-activating complex. Biochimie 84, 203–214, 2002. doi:https://doi.org/10.1016/S0300-9084(02)01376-7.
   PubMed Web of Science ®Google Scholar
• Travaglini-Allocatelli C: Protein machineries involved in the attachment of heme to cytochrome c: protein structures and molecular mechanisms. Scientifica (Cairo) 2013, 505714, 2013. doi:10.1155/2013/505714.
   PubMedGoogle Scholar
• Kim HJ, Khalimonchuk O, Smith PM, and Winge DR: Structure, function, and assembly of heme centers in mitochondrial respiratory complexes. Biochim Biophys Acta (BBA)-Mol Cell Res 1823, 1604–1616, 2012.
   PubMed Web of Science ®Google Scholar
• Longpre J and Loo G: Inhibition of deoxycholate-induced apoptosis in iron-depleted HCT-116 cells. Apoptosis 17, 70–78, 2012.
   PubMed Web of Science ®Google Scholar
• de Deungria M, Rao R, Wobken JD, Luciana M, Nelson CA, et al.: Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain. Pediatr Res 48, 169–176, 2000. doi:10.1203/00006450-200008000-00009.
   PubMed Web of Science ®Google Scholar
• Payne CM, Holubec H, Bernstein C, Bernstein H, Dvorak K, et al.: Crypt-restricted loss and decreased protein expression of cytochrome C oxidase subunit I as potential hypothesis-driven biomarkers of colon cancer risk. Cancer Epidemiol Biomarkers Prev 14, 2066–2075, 2005. doi:10.1158/1055-9965.epi-05-0180.
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhang W, Ma SF, Miasniakova G, Sergueeva A, et al.: Iron deficiency modifies gene expression variation induced by augmented hypoxia sensing. Blood Cells Mol Dis 52, 35–45, 2014. doi:10.1016/j.bcmd.2013.07.016.
   PubMed Web of Science ®Google Scholar
• Nebert DW and Russell DW: Clinical importance of the cytochromes P450. Lancet 360, 1155–1162, 2002. doi:10.1016/s0140-6736(02)11203-7.
   PubMed Web of Science ®Google Scholar
• Sheweita SA: Drug-metabolizing enzymes: mechanisms and functions. Curr Drug Metab 1, 107–132, 2000.
   PubMed Web of Science ®Google Scholar
• Oates PS and West AR: Heme in intestinal epithelial cell turnover, differentiation, detoxification, inflammation, carcinogenesis, absorption and motility. World J Gastroenterol: WJG 12, 4281–4295, 2006.
   PubMed Web of Science ®Google Scholar
• McLean KJ, Luciakova D, Belcher J, Tee KL, and Munro AW: Biological diversity of cytochrome P450 redox partner systems. Adv Exp Med Biol 851, 299–317, 2015. doi:10.1007/978-3-319-16009-2_11.
   PubMed Web of Science ®Google Scholar
• Dhur A, Galan P, and Hercberg S: Effects of different degrees of iron deficiency on cytochrome P450 complex and pentose phosphate pathway dehydrogenases in the rat. J Nutr 119, 40–47, 1989.
   PubMed Web of Science ®Google Scholar
• Rao NJ and Jagadeesan V: Effect of long term iron deficiency on the activities of hepatic and extra-hepatic drug metabolising enzymes in Fischer rats. Comp Biochem Physiol Part B: Biochem Mol Biol 110, 167–173, 1995.
   PubMed Web of Science ®Google Scholar
• Yang C, Li C, Li M, Tong X, Hu X, et al.: CYP2S1 depletion enhances colorectal cell proliferation is associated with PGE2-mediated activation of β-catenin signaling. Exp Cell Res 331, 377–386, 2015.
   PubMed Web of Science ®Google Scholar
• Alam J and Cook JL: Transcriptional regulation of the heme oxygenase-1 gene via the stress response element pathway. Curr Pharm Des 9, 2499–2511, 2003.
   PubMed Web of Science ®Google Scholar
• Gozzelino R, Jeney V, and Soares MP: Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol 50, 323–354, 2010.
   PubMed Web of Science ®Google Scholar
• Clérigues V, Guillén MI, Castejón MA, Gomar F, Mirabet V, et al.: Heme oxygenase-1 mediates protective effects on inflammatory, catabolic and senescence responses induced by interleukin-1β in osteoarthritic osteoblasts. Biochem Pharmacol 83, 395–405, 2012.
   PubMed Web of Science ®Google Scholar
• Lai C and Loo G: Cellular iron depletion weakens induction of heme oxygenase-1 by cadmium. Int J Biochem Cell Biol 43, 88–97, 2011.
   PubMed Web of Science ®Google Scholar
• D'Ignazio L, Bandarra D, and Rocha S: NF-kappaB and HIF crosstalk in immune responses. Febs J 2015. doi:10.1111/febs.13578.
   PubMed Web of Science ®Google Scholar
• Kurpios-Piec D, Grosicka-Maciag E, Wozniak K, Kowalewski C, Kiernozek E, et al.: Thiram activates NF-kappaB and enhances ICAM-1 expression in human microvascular endothelial HMEC-1 cells. Pestic Biochem Physiol 118, 82–89, 2015. doi:10.1016/j.pestbp.2014.12.003.
   PubMed Web of Science ®Google Scholar
• Milstone DS, Ilyama M, Chen M, O'Donnell P, Davis VM, et al.: Differential role of an NF-kappaB transcriptional response element in endothelial versus intimal cell VCAM-1 expression. Circ Res 117, 166–177, 2015. doi:10.1161/circresaha.117.306666.
   PubMed Web of Science ®Google Scholar
• Kim HR, Shin da Y, and Chung KH: The role of NF-kappaB signaling pathway in polyhexamethylene guanidine phosphate induced inflammatory response in mouse macrophage RAW264.7 cells. Toxicol Lett 233, 148–155, 2015. doi:10.1016/j.toxlet.2015.01.005.
   PubMed Web of Science ®Google Scholar
• Brightbill HD, Jackman JK, Suto E, Kennedy H, Jones C, 3rd, et al.: Conditional deletion of NF-kappaB-Inducing Kinase (NIK) in adult mice disrupts mature B cell survival and activation. J Immunol 195, 953–964, 2015. doi:10.4049/jimmunol.1401514.
   PubMed Web of Science ®Google Scholar
• Ahn G, Park E, Park HJ, Jeon YJ, Lee J, et al.: The classical NFkappaB pathway is required for phloroglucinol-induced activation of murine lymphocytes. Biochim Biophys Acta 1800, 639–645, 2010. doi:10.1016/j.bbagen.2010.03.014.
   PubMed Web of Science ®Google Scholar
• Fluck K, Breves G, Fandrey J, and Winning S: Hypoxia-inducible factor 1 in dendritic cells is crucial for the activation of protective regulatory T cells in murine colitis. Mucosal Immunol 2015. doi:10.1038/mi.2015.67.
   PubMed Web of Science ®Google Scholar
• Zhu F, Yue W, and Wang Y: The nuclear factor kappa B (NF-kappaB) activation is required for phagocytosis of staphylococcus aureus by RAW 264.7 cells. Exp Cell Res 327, 256–263, 2014. doi:10.1016/j.yexcr.2014.04.018.
   PubMed Web of Science ®Google Scholar
• Gutierrez MG, Mishra BB, Jordao L, Elliott E, Anes E, et al.: NF-kappa B activation controls phagolysosome fusion-mediated killing of mycobacteria by macrophages. J Immunol 181, 2651–2663, 2008.
   PubMed Web of Science ®Google Scholar
• Wang L and Cherayil BJ: Ironing out the wrinkles in host defense: interactions between iron homeostasis and innate immunity. J Innate Immun 1, 455–464, 2009. doi:10.1159/000210016.
   PubMed Web of Science ®Google Scholar
• Paino IM, Miranda JC, Marzocchi-Machado CM, Cesarino EJ, de Castro FA, et al.: Phagocytosis, oxidative burst, and produced reactive species are affected by iron deficiency anemia and anemia of chronic diseases in elderly. Biol Trace Elem Res 129, 116–125, 2009. doi:10.1007/s12011-008-8303-8.
   PubMed Web of Science ®Google Scholar
• Winterbourn CC, Kettle AJ, and Hampton MB: Reactive oxygen species and neutrophil function. Annu Rev Biochem 2016.
   PubMed Web of Science ®Google Scholar
• Yamaguchi R, Kawata J, Yamamoto T, Ishimaru Y, Sakamoto A, et al.: Mechanism of interferon-gamma production by monocytes stimulated with myeloperoxidase and neutrophil extracellular traps. Blood Cells Mol Dis 55, 127–133, 2015. doi:10.1016/j.bcmd.2015.05.012.
   PubMed Web of Science ®Google Scholar
• Bergman M, Salman H, Pinchasi R, Straussberg R, Djaldetti M, et al.: Phagocytic capacity and apoptosis of peripheral blood cells from patients with iron deficiency anemia. Biomed Pharmacother 59, 307–311, 2005.
   PubMed Web of Science ®Google Scholar
• Kurtoglu E, Ugur A, Baltaci AK, Mogolkoc R, and Undar L: Activity of neutrophil NADPH oxidase in iron-deficient anemia. Biol Trace Elem Res 96, 109–115, 2003.
   PubMed Web of Science ®Google Scholar
• Anand RJ, Gribar SC, Li J, Kohler JW, Branca MF, et al.: Hypoxia causes an increase in phagocytosis by macrophages in a HIF-1alpha-dependent manner. J Leukoc Biol 82, 1257–1265, 2007. doi:10.1189/jlb.0307195.
   PubMed Web of Science ®Google Scholar
• Shirato K, Kizaki T, Sakurai T, Ogasawara JE, Ishibashi Y, et al.: Hypoxia-inducible factor-1alpha suppresses the expression of macrophage scavenger receptor 1. Pflugers Arch 459, 93–103, 2009. doi:10.1007/s00424-009-0702-y.
   PubMed Web of Science ®Google Scholar
• Moretta L, Montaldo E, Vacca P, Del Zotto G, Moretta F, et al.: Human natural killer cells: origin, receptors, function, and clinical applications. Int Arch Allergy Immunol 164, 253–264, 2014. doi:10.1159/000365632.
   PubMed Web of Science ®Google Scholar
• Sarkar S, Germeraad WT, Rouschop KM, Steeghs EM, van Gelder M, et al.: Hypoxia induced impairment of NK cell cytotoxicity against multiple myeloma can be overcome by IL-2 activation of the NK cells. PLoS One 8, e64835, 2013. doi:10.1371/journal.pone.0064835.
   PubMed Web of Science ®Google Scholar
• Balsamo M, Manzini C, Pietra G, Raggi F, Blengio F, et al.: Hypoxia downregulates the expression of activating receptors involved in NK-cell-mediated target cell killing without affecting ADCC. Eur J Immunol 43, 2756–2764, 2013. doi:10.1002/eji.201343448.
   PubMed Web of Science ®Google Scholar
• Schilling D, Tetzlaff F, Konrad S, Li W, and Multhoff G: A hypoxia-induced decrease of either MICA/B or Hsp70 on the membrane of tumor cells mediates immune escape from NK cells. Cell Stress Chaperones 20, 139–147, 2015. doi:10.1007/s12192-014-0532-5.
   PubMed Web of Science ®Google Scholar
• Baginska J, Viry E, Berchem G, Poli A, Noman MZ, et al.: Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia. Proc Natl Acad Sci U S A 110, 17450–17455, 2013. doi:10.1073/pnas.1304790110.
   PubMed Web of Science ®Google Scholar
• Bowlus CL: The role of iron in T cell development and autoimmunity. Autoimmun Rev 2, 73–78, 2003.
   PubMed Web of Science ®Google Scholar
• Kuvibidila SR and Porretta C: Iron deficiency and in vitro iron chelation reduce the expression of cluster of differentiation molecule (CD)28 but not CD3 receptors on murine thymocytes and spleen cells. Br J Nutr 90, 179–189, 2003.
   PubMed Web of Science ®Google Scholar
• Kuvibidila SR, Porretta C, Surendra Baliga B, and Leiva LE: Reduced thymocyte proliferation but not increased apoptosis as a possible cause of thymus atrophy in iron-deficient mice. Br J Nutr 86, 157–162, 2001.
   PubMed Web of Science ®Google Scholar
• Zimmermann MB: The influence of iron status on iodine utilization and thyroid function. Annu Rev Nutr 26, 367–389, 2006.
   PubMed Web of Science ®Google Scholar
• Kuvibidila SR, Kitchens D, and Baliga BS: In vivo and in vitro iron deficiency reduces protein kinase C activity and translocation in murine splenic and purified T cells. J Cell Biochem 74, 468–478, 1999.
   PubMed Web of Science ®Google Scholar
• Klecha AJ, Salgueiro J, Wald M, Boccio J, Zubillaga M, et al.: In vivo iron and zinc deficiency diminished T- and B-selective mitogen stimulation of murine lymphoid cells through protein kinase C-mediated mechanism. Biol Trace Elem Res 104, 173–183, 2005. doi:10.1385/bter:104:2:173.
   PubMed Web of Science ®Google Scholar
• Kuvibidila S and Warrier RP: Differential effects of iron deficiency and underfeeding on serum levels of interleukin-10, interleukin-12p40, and interferon-gamma in mice. Cytokine 26, 73–81, 2004.
   PubMed Web of Science ®Google Scholar
• Kuvibidila S, Yu L, Ode D, Velez M, Gardner R, et al.: Effects of iron deficiency on the secretion of interleukin-10 by mitogen-activated and non-activated murine spleen cells. J Cell Biochem 90, 278–286, 2003. doi:10.1002/jcb.10627.
   PubMed Web of Science ®Google Scholar
• Kuvibidila SR, Velez M, Gardner R, Penugonda K, Chandra LC, et al.: Iron deficiency reduces serum and in vitro secretion of interleukin-4 in mice independent of altered spleen cell proliferation. Nutr Res 32, 107–115, 2012. doi:10.1016/j.nutres.2011.12.005.
   PubMed Web of Science ®Google Scholar