Abstract
Esophageal cancer is one of the leading causes of cancer death and the seventh most prevalent cancer worldwide. Considering the positive association of high selenium with the prevalence of esophageal cancer, we have investigated the effect of high doses of selenium on gene expression in the normal esophageal tissue of rats. Twenty male rats were randomly divided into four groups: control group, group 2 mg Se/L, 10 mg Se/L, and 20 mg Se/L rats fed with a basal basic diet and 2, 10, and 20 mg Se/L as sodium selenite in drinking water, respectively, for 20 weeks. Serum malondialdehyde and glutathione peroxidase activity were measured. Moreover, the expression and concentration of the cyclin D1, cyclin E, KRAS, p53, NF-kB, TGF-β, and MGMT in the esophageal tissue were analyzed and compared between the four groups. In normal esophageal tissue, selenium supplementations (2, 10, and 20 mg Se/L) increased the mRNA levels of cyclin D1, P53, KRAS, NF-κB p65, and MGMT and decreased the mRNA level of TGFß1. The concentrations of cyclin D1 and MGMT were also significantly increased by selenium supplementations. Selenium supplementations had no significant effect on serum MDA but significantly increased GPX activity. The present study suggests that selenium supplementation (2, 10, and 20 mg Se/L) affects gene expression related to inflammation, Cell proliferation, and apoptosis in the normal esophageal tissue. However, there were no observed abnormalities other than reduced growth with supplementation of 20 mg/L as Na2SeO3 in rats.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin 70(1):7–30. https://doi.org/10.3322/caac.21590
Arnold M, Soerjomataram I, Ferlay J, Forman D (2015) Global incidence of oesophageal cancer by histological subtype in 2012. Gut 64(3):381–387. https://doi.org/10.1136/gutjnl-2014-308124
Arnold M, Ferlay J, van Berge Henegouwen MI, Soerjomataram I (2020) Global burden of oesophageal and gastric cancer by histology and subsite in 2018. Gut 69(9):1564–1571. https://doi.org/10.1136/gutjnl-2020-321600
Thrift AP (2021) Global burden and epidemiology of Barrett oesophagus and oesophageal cancer. Nat Rev Gastroenterol Hepatol 18(6):432–443. https://doi.org/10.1038/s41575-021-00419-3
Roman M, Jitaru P, Barbante C (2014) Selenium biochemistry and its role for human health. Metallomics 6(1):25–54. https://doi.org/10.1039/c3mt00185g
Lee KH, Jeong D (2012) Bimodal actions of selenium essential for antioxidant and toxic pro-oxidant activities: the selenium paradox (Review). Mol Med Rep 5(2):299–304. https://doi.org/10.3892/mmr.2011.651
Razaghi A, Poorebrahim M, Sarhan D, Björnstedt M (2021) Selenium stimulates the antitumour immunity: Insights to future research. Eur J Cancer 155:256–267. https://doi.org/10.1016/j.ejca.2021.07.013
Ganther HE (1999) Selenium metabolism, selenoproteins and mechanisms of cancer prevention: complexities with thioredoxin reductase. Carcinogenesis 20(9):1657–1666. https://doi.org/10.1093/carcin/20.9.1657
Kalyanaraman B, Cheng G, Hardy M, Ouari O, Bennett B, Zielonka J (2018) Teaching the basics of reactive oxygen species and their relevance to cancer biology: Mitochondrial reactive oxygen species detection, redox signaling, and targeted therapies. Redox Biol 15:347–362. https://doi.org/10.1016/j.redox.2017.12.012
Kieliszek M (2019) Selenium-Fascinating Microelement, Properties and Sources in Food. Molecules 24 (7). https://doi.org/10.3390/molecules24071298
Kuria A, Fang X, Li M, Han H, He J, Aaseth JO, Cao Y (2020) Does dietary intake of selenium protect against cancer? A systematic review and meta-analysis of population-based prospective studies. Crit Rev Food Sci Nutr 60(4):684–694. https://doi.org/10.1080/10408398.2018.1548427
Kuršvietienė L, Mongirdienė A, Bernatonienė J, Šulinskienė J, Stanevičienė I (2020) Selenium Anticancer Properties and Impact on Cellular Redox Status. Antioxidants (Basel) 9(1). https://doi.org/10.3390/antiox9010080
Radomska D, Czarnomysy R, Radomski D, Bielawska A, Bielawski K (2021) Selenium as a Bioactive Micronutrient in the Human Diet and Its Cancer Chemopreventive Activity. Nutrients 13(5). https://doi.org/10.3390/nu13051649
Vinceti M, Filippini T, Cilloni S, Crespi CM (2017) The Epidemiology of Selenium and Human Cancer. Adv Cancer Res 136:1–48. https://doi.org/10.1016/bs.acr.2017.07.001
Vinceti M, Vicentini M, Wise LA, Sacchettini C, Malagoli C, Ballotari P, Filippini T, Malavolti M, Rossi PG (2018) Cancer incidence following long-term consumption of drinking water with high inorganic selenium content. Sci Total Environ 635:390–396. https://doi.org/10.1016/j.scitotenv.2018.04.097
Appleton J, Zhang Q, Green K, Zhang G, Ge X, Liu X, Li JX (2006) Selenium in soil, grain, human hair and drinking water in relation to esophageal cancer in the Cixian area, Hebei Province, People’s Republic of China. Appl Geochem 21(4):684–700
Semnani S, Roshandel G, Zendehbad A, Keshtkar A, Rahimzadeh H, Abdolahi N, Besharat S, Moradi A, Mirkarimi H, Hasheminasab S (2010) Soils selenium level and esophageal cancer: an ecological study in a high risk area for esophageal cancer. J Trace Elem Med Biol 24(3):174–177. https://doi.org/10.1016/j.jtemb.2010.03.002
Rahimzadeh-Barzoki H, Joshaghani H, Beirami S, Mansurian M, Semnani S, Roshandel G (2014) Selenium levels in rice samples from high and low risk areas for esophageal cancer. Saudi Med J 35(6):617–620
Keshavarzi B, Moore F, Najmeddin A, Rahmani F (2012) The role of selenium and selected trace elements in the etiology of esophageal cancer in high risk Golestan province of Iran. Sci Total Environ 433:89–97. https://doi.org/10.1016/j.scitotenv.2012.04.033
Pritchett NR, Burgert SL, Murphy GA, Brockman JD, White RE, Lando J, Chepkwony R, Topazian MD, Abnet CC, Dawsey SM, Mwachiro MM (2017) Cross sectional study of serum selenium concentration and esophageal squamous dysplasia in western Kenya. BMC Cancer 17(1):835. https://doi.org/10.1186/s12885-017-3837-9
Eslami Z, Mirghani SJ, Moghanlou AE, Norouzi A, Naseh H, Joshaghani H, Peres WAF, Younesian O, Hosseinzadeh S, Bideskan JA (2021) An efficient model of non-alcoholic fatty liver disease (NAFLD) versus current experimental models: effects of fructose, fat, and carbon tetrachloride on NAFLD. Hepat Mon 21(8):e117696. https://doi.org/10.5812/hepatmon.117696
Younesian O, Khodabakhshi B, Abdolahi N, Norouzi A, Behnampour N, Hosseinzadeh S, Alarzi SSH, Joshaghani H (2021) Decreased Serum Selenium Levels of COVID-19 Patients in Comparison with Healthy Individuals. Biol Trace Elem Res:1–6. https://doi.org/10.1007/s12011-021-02797-w
Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70(1):158–169
Kostner K, Hornykewycz S, Yang P, Neunteufl T, Glogar D, Weidinger F, Maurer G, Huber K (1997) Is oxidative stress causally linked to unstable angina pectoris? A study in 100 CAD patients and matched controls. Cardiovasc Res 36(3):330–336. https://doi.org/10.1016/s0008-6363(97)00185-5
Raines AM, Sunde RA (2011) Selenium toxicity but not deficient or super-nutritional selenium status vastly alters the transcriptome in rodents. BMC Genomics 12:26. https://doi.org/10.1186/1471-2164-12-26
Hu X, Chandler JD, Orr ML, Hao L, Liu K, Uppal K, Go YM, Jones DP (2018) Selenium Supplementation Alters Hepatic Energy and Fatty Acid Metabolism in Mice. J Nutr 148(5):675–684. https://doi.org/10.1093/jn/nxy036
Barchielli G, Capperucci A, Tanini D (2022) The Role of Selenium in Pathologies: An Updated Review. Antioxidants (Basel) 11(2). https://doi.org/10.3390/antiox11020251
Chen X, Mikhail SS, Ding YW, Yang G, Bondoc F, Yang CS (2000) Effects of vitamin E and selenium supplementation on esophageal adenocarcinogenesis in a surgical model with rats. Carcinogenesis 21(8):1531–1536
Xie B, Lin J, Sui K, Huang Z, Chen Z, Hang W (2019) Differential diagnosis of multielements in cancerous and non-cancerous esophageal tissues. Talanta 196:585–591. https://doi.org/10.1016/j.talanta.2018.12.061
Nozadi F, Azadi N, Mansouri B, Tavakoli T, Mehrpour O (2021) Association between trace element concentrations in cancerous and non-cancerous tissues with the risk of gastrointestinal cancers in Eastern Iran. Environ Sci Pollut Res Int 28(44):62530–62540. https://doi.org/10.1007/s11356-021-15224-3
Liou GY, Döppler H, DelGiorno KE, Zhang L, Leitges M, Crawford HC, Murphy MP, Storz P (2016) Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions. Cell Rep 14(10):2325–2336. https://doi.org/10.1016/j.celrep.2016.02.029
Dobrovolskaia MA, Kozlov SV (2005) Inflammation and cancer: when NF-kappaB amalgamates the perilous partnership. Curr Cancer Drug Targets 5(5):325–344. https://doi.org/10.2174/1568009054629645
Kang MR, Kim MS, Kim SS, Ahn CH, Yoo NJ, Lee SH (2009) NF-kappaB signalling proteins p50/p105, p52/p100, RelA, and IKKepsilon are over-expressed in oesophageal squamous cell carcinomas. Pathology 41(7):622–625. https://doi.org/10.3109/00313020903257756
Ledoux AC, Perkins ND (2014) NF-κB and the cell cycle. Biochem Soc Trans 42(1):76–81. https://doi.org/10.1042/bst20130156
Shi Y, Li MY, Wang H, Li C, Liu WY, Gao YM, Wang B, Song JW, Ma YQ (2022) The Relationship between MACC1/c-Met/Cyclin D1 Axis Expression and Prognosis in ESCC. Anal Cell Pathol (Amst) 2022:9651503. https://doi.org/10.1155/2022/9651503
Ferino A, Rapozzi V, Xodo LE (2020) The ROS-KRAS-Nrf2 axis in the control of the redox homeostasis and the intersection with survival-apoptosis pathways: Implications for photodynamic therapy. J Photochem Photobiol B 202:111672. https://doi.org/10.1016/j.jphotobiol.2019.111672
Kannan K, Jain SK (2000) Oxidative stress and apoptosis. Pathophysiology 7(3):153–163. https://doi.org/10.1016/s0928-4680(00)00053-5
Vousden KH, Lu X (2002) Live or let die: the cell’s response to p53. Nat Rev Cancer 2(8):594–604. https://doi.org/10.1038/nrc864
Shibata-Kobayashi S, Yamashita H, Okuma K, Shiraishi K, Igaki H, Ohtomo K, Nakagawa K (2013) Correlation among 16 biological factors [p53, p21(waf1), MIB-1 (Ki-67), p16(INK4A), cyclin D1, E-cadherin, Bcl-2, TNF-α, NF-κB, TGF-β, MMP-7, COX-2, EGFR, HER2/neu, ER, and HIF-1α] and clinical outcomes following curative chemoradiation therapy in 10 patients with esophageal squamous cell carcinoma. Oncol Lett 5(3):903–910. https://doi.org/10.3892/ol.2013.1130
Kok DE, Kiemeney LA, Verhaegh GW, Schalken JA, van Lin EN, Sedelaar JP, Witjes JA, Hulsbergen-van de Kaa CA, van ‘t Veer P, Kampman E, Afman LA (2017) A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate. Oncotarget 8(6):10565–10579. https://doi.org/10.18632/oncotarget.14551
Christmann M, Verbeek B, Roos WP, Kaina B (2011) O(6)-Methylguanine-DNA methyltransferase (MGMT) in normal tissues and tumors: enzyme activity, promoter methylation and immunohistochemistry. Biochim Biophys Acta 1816(2):179–190. https://doi.org/10.1016/j.bbcan.2011.06.002
Jabłońska E, Reszka E (2017) Selenium and Epigenetics in Cancer: Focus on DNA Methylation. Adv Cancer Res 136:193–234. https://doi.org/10.1016/bs.acr.2017.07.002
Galan-Chilet I, Tellez-Plaza M, Guallar E, De Marco G, Lopez-Izquierdo R, Gonzalez-Manzano I, Carmen Tormos M, Martin-Nuñez GM, Rojo-Martinez G, Saez GT, Martín-Escudero JC, Redon J, Javier Chaves F (2014) Plasma selenium levels and oxidative stress biomarkers: a gene-environment interaction population-based study. Free Radical Biol Med 74:229–236. https://doi.org/10.1016/j.freeradbiomed.2014.07.005
Grotto D, Carneiro MFH, de Castro MM, Garcia SC, Barbosa Junior F (2018) Long-Term Excessive Selenium Supplementation Induces Hypertension in Rats. Biol Trace Elem Res 182(1):70–77. https://doi.org/10.1007/s12011-017-1076-1
Sunde RA, Li JL, Taylor RM (2016) Insights for Setting of Nutrient Requirements, Gleaned by Comparison of Selenium Status Biomarkers in Turkeys and Chickens versus Rats, Mice, and Lambs. Adv Nutr (Bethesda, Md) 7(6):1129–1138. https://doi.org/10.3945/an.116.012872
Acknowledgements
These data are extracted from the Ph.D thesis submitted by Ommolbanin Younesian by grant number 111215, which was supported by Golestan University of Medical Sciences, Golestan province, Gorgan, Iran.
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Younesian, O., Sheikh Arabi, M., Jafari, S.M. et al. Long-Term Excessive Selenium Supplementation Affects Gene Expression in Esophageal Tissue of Rats. Biol Trace Elem Res 201, 3387–3394 (2023). https://doi.org/10.1007/s12011-022-03413-1
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DOI: https://doi.org/10.1007/s12011-022-03413-1