Intestinal Iron Homeostasis and Colon Tumorigenesis

Overview

Journal Nutrients

Date 2013 Jul 2

PMID 23812305

Citations 37

Authors

Xiang Xue

Yatrik M Shah

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.

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References

Glei M, Latunde-Dada G, Klinder A, Becker T, Hermann U, Voigt K . Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A. Mutat Res. 2002; 519(1-2):151-61. DOI: 10.1016/s1383-5718(02)00135-3. View

Liang S, Richardson D . The effect of potent iron chelators on the regulation of p53: examination of the expression, localization and DNA-binding activity of p53 and the transactivation of WAF1. Carcinogenesis. 2003; 24(10):1601-14. DOI: 10.1093/carcin/bgg116. View

Zimmermann M, Chassard C, Rohner F, NGoran E, Nindjin C, Dostal A . The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr. 2010; 92(6):1406-15. DOI: 10.3945/ajcn.110.004564. View

Dostal A, Chassard C, Hilty F, Zimmermann M, Jaeggi T, Rossi S . Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats. J Nutr. 2011; 142(2):271-7. PMC: 3260059. DOI: 10.3945/jn.111.148643. View

Osborne N, Gurrin L, Allen K, Constantine C, Delatycki M, McLaren C . HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology. 2010; 51(4):1311-8. PMC: 3815603. DOI: 10.1002/hep.23448. View

cermak J, Balla J, JACOB H, Balla G, Enright H, Nath K . Tumor cell heme uptake induces ferritin synthesis resulting in altered oxidant sensitivity: possible role in chemotherapy efficacy. Cancer Res. 1993; 53(21):5308-13. View

Cross A, Ferrucci L, Risch A, Graubard B, Ward M, Park Y . A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cancer Res. 2010; 70(6):2406-14. PMC: 2840051. DOI: 10.1158/0008-5472.CAN-09-3929. View

Ward D, Roberts K, Brookes M, Joy H, Martin A, Ismail T . Increased hepcidin expression in colorectal carcinogenesis. World J Gastroenterol. 2008; 14(9):1339-45. PMC: 2693679. DOI: 10.3748/wjg.14.1339. View

Gunshin H, Fujiwara Y, Custodio A, Direnzo C, Robine S, Andrews N . Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J Clin Invest. 2005; 115(5):1258-66. PMC: 1077176. DOI: 10.1172/JCI24356. View

10.

Ganz T, Nemeth E . Hepcidin and disorders of iron metabolism. Annu Rev Med. 2010; 62:347-60. DOI: 10.1146/annurev-med-050109-142444. View

11.

Zhang F, Tao Y, Zhang Z, Guo X, An P, Shen Y . Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses. Haematologica. 2012; 97(12):1826-35. PMC: 3590089. DOI: 10.3324/haematol.2012.063974. View

12.

Kinzler K, Vogelstein B . Lessons from hereditary colorectal cancer. Cell. 1996; 87(2):159-70. DOI: 10.1016/s0092-8674(00)81333-1. View

13.

Ijssennagger N, Derrien M, van Doorn G, Rijnierse A, van den Bogert B, Muller M . Dietary heme alters microbiota and mucosa of mouse colon without functional changes in host-microbe cross-talk. PLoS One. 2012; 7(12):e49868. PMC: 3519815. DOI: 10.1371/journal.pone.0049868. View

14.

Sesink A, Termont D, Kleibeuker J, van der Meer R . Red meat and colon cancer: dietary haem, but not fat, has cytotoxic and hyperproliferative effects on rat colonic epithelium. Carcinogenesis. 2000; 21(10):1909-15. DOI: 10.1093/carcin/21.10.1909. View

15.

Calzolari A, Oliviero I, Deaglio S, Mariani G, Biffoni M, Sposi N . Transferrin receptor 2 is frequently expressed in human cancer cell lines. Blood Cells Mol Dis. 2007; 39(1):82-91. DOI: 10.1016/j.bcmd.2007.02.003. View

16.

ODonnell K, Yu D, Zeller K, Kim J, Racke F, Thomas-Tikhonenko A . Activation of transferrin receptor 1 by c-Myc enhances cellular proliferation and tumorigenesis. Mol Cell Biol. 2006; 26(6):2373-86. PMC: 1430295. DOI: 10.1128/MCB.26.6.2373-2386.2006. View

17.

Knutson M . Iron-sensing proteins that regulate hepcidin and enteric iron absorption. Annu Rev Nutr. 2010; 30:149-71. DOI: 10.1146/annurev.nutr.012809.104801. View

18.

Okazaki F, Matsunaga N, Okazaki H, Utoguchi N, Suzuki R, Maruyama K . Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice. Cancer Res. 2010; 70(15):6238-46. DOI: 10.1158/0008-5472.CAN-10-0184. View

19.

Roughead Z, Zito C, Hunt J . Inhibitory effects of dietary calcium on the initial uptake and subsequent retention of heme and nonheme iron in humans: comparisons using an intestinal lavage method. Am J Clin Nutr. 2005; 82(3):589-97. DOI: 10.1093/ajcn.82.3.589. View

20.

Baradat M, Jouanin I, Dalleau S, Tache S, Gieules M, Debrauwer L . 4-Hydroxy-2(E)-nonenal metabolism differs in Apc(+/+) cells and in Apc(Min/+) cells: it may explain colon cancer promotion by heme iron. Chem Res Toxicol. 2011; 24(11):1984-93. DOI: 10.1021/tx2003036. View