The Inhibitory Effect of Selenium Supplementation on Tumor Progression in a DMBA-Induced Breast Cancer Model in Wistar Rats

Nour EL-Houda Feriel Djebara (1) , Adel Gouri (2) , Houari Hemida (3) , Chahinaise Zaoui (4) , Bachir Benarba (5)
(1) Laboratory Research on Biological Systems and Geomatics, Faculty of Nature and Life, University of Mascara. , Algeria
(2) Laboratory of Biochemistry, Faculty of Medicine, Badji Mokhtar University, Annaba, Algeria. , Algeria
(3) Department of Biomedicine, Institute of veterinary sciences, University of Tiaret, Algeria. , Algeria
(4) Laboratory of Developmental Biology and Differentiation. Faculty of Natural and Life Sciences, ORAN 1 University and Department of Pharmacy, Faculty of Medicine, Oran 1 University. , Algeria
(5) Laboratory Research on Biological Systems and Geomatics, Faculty of Nature and Life, University of Mascara, Algeria , Algeria

Abstract

Background: Breast cancer remains a significant global public health concern, necessitating the ongoing exploration of novel preventive and therapeutic strategies. Selenium supplementation has been proposed as a potential chemopreventive agent, yet its efficacy lacks robust in vivo validation.


Aims: This study aimed to evaluate the chemopreventive potential of selenium supplementation and its effect on tumor progression in a 7,12-dimethylbenz[a]anthracene DMBA-induced breast cancer model in Wistar rats. 


Methods: Twenty-four adult female Wister rat were allocated into four experimental groups (n=6): Control (vehicle only); DMBA (carcinogen control); DMBA + Se 200 µg/kg; and DMBA + Se 400 µg/kg. Mammary tumors were induced via a single intragastric administration of DMBA (80 mg/kg). Over a 23-week period, hematological, biochemical, and histopathological analyses were conducted. The volume of excised mammary tumors was measured post-sacrifice.


Results: Supplementation with selenium at a dose of 400 µg/kg resulted in a statistically significant reduction in mean tumor volume (0.13 cm³) compared to the DMBA-only group (1.32 cm³). Concurrently, this high-dose group exhibited significant amelioration in serum levels of specific biochemical markers including aspartate aminotransferase (AST), urea, and creatinine. Histopathological assessment further supported these findings, revealing a more preserved mammary tissue architecture in rats receiving the high-dose selenium.


Conclusions: While selenium supplementation at 400 µg/Kg demonstrated a significant inhibition effect on tumor progression and conferred hepatorenal protection, a definitive chemopreventive effect against DMBA-induced carcinogenesis was not established. These results indicate that selenium may function as a therapeutic modulator rather than a primary preventive agent in this model. Further investigation employing higher doses and alternative administration regimens is warranted to elucidate its full chemopreventive potential.


Keywords: Breast cancer; Selenium; DMBA, Chemoprevention, Tumor Progression; Wistar rats.

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References

Akhouri, V., Kumari, M., & Kumar, A. (2020). Therapeutic effect of Aegle marmelos fruit extract against DMBA induced breast cancer in rats. Scientific Reports, 10(1), 18016. https://doi.org/10.1038/s41598-020-72935-2
Baltaci, S. B., Mogulkoc, R., Baltaci, A. K., Emsen, A., & Artac, H. (2018). The effect of zinc and melatonin supplementation on immunity parameters in breast cancer induced by DMBA in rats. Archives of Physiology and Biochemistry, 124(3), 247–252. https://doi.org/10.1080/13813455.2017.1392580
Cai, X., Wang, C., Yu, W., Fan, W., Wang, S., Shen, N., Wu, P., Li, X., & Wang, F. (2016). Selenium exposure and cancer risk: An updated meta-analysis and meta-regression. Scientific Reports, 6(1), 19213. https://doi.org/10.1038/srep19213
Cardoso, B. R., Roberts, B. R., Bush, A. I., & Hare, D. J. (2015). Selenium, selenoproteins and neurodegenerative diseases. Metallomics. Integrated Biometal Science, 7(8), 1213–1228. https://doi.org/10.1039/c5mt00075k
Çay, M., & Naziroğlu, M. (1999). Effects of intraperitoneally-administered vitamin E and selenium on the blood biochemical and haematological parameters in rats. Cell Biochemistry and Function, 17(2), 143-148. https://doi.org/10.1002/(sici)1099-0844(199906)17:2<143::aid-cbf802>3.0.co;2-h
Charalabopoulos, K., Kotsalos, A., Batistatou, A., Charalabopoulos, A., Vezyraki, P., Peschos, D., Kalfakakou, V., & Evangelou, A. (2006). Selenium in serum and neoplastic tissue in breast cancer: correlation with CEA. British Journal of Cancer, 95(6), 674–676. https://doi.org/10.1038/sj.bjc.6603292
Cinato, M., Andersson, L., Miljanovic, A., Laudette, M., Kunduzova, O., Borén, J., & Levin, M. C. (2024). Role of perilipins in oxidative stress-implications for cardiovascular disease. Antioxidants (Basel, Switzerland), 13(2), 209. https://doi.org/10.3390/antiox13020209
El-Bayoumy, K. (2001). The protective role of selenium on genetic damage and on cancer. Mutation Research, 475(1–2), 123–139. https://doi.org/10.1016/s0027-5107(01)00075-6
El makawy, A. I., Mabrouk, D. M., Mohammed, S. E., Abdel-Aziem, S. H., EL-Kader, H. A. A., Sharaf, H. A., Youssef, D. A., & Ibrahim, F. M. (2022). The suppressive role of nanoencapsulated chia oil against DMBA-induced breast cancer through oxidative stress repression and tumor genes expression modulation in rats. Molecular Biology Reports, 49(11), 10217–10228. https://doi.org/10.1007/s11033-022-07885-1
Elen, A., & Turan, M. K. (2019). Classifying white blood cells using machine learning algorithms. Uluslararası Muhendislik Arastirma ve Gelistirme Dergisi, 141–152. https://doi.org/10.29137/umagd.498372
Fontelles, C. C., & Ong, T. P. (2017). Selenium and breast cancer risk: Focus on cellular and molecular mechanisms. Advances in Cancer Research, 136, 173–192. https://doi.org/10.1016/bs.acr.2017.08.001
Gamal, H., Tawfik, W., El-Sayyad, H. I., Emam, A. N., Fahmy, H. M., & El-Ghaweet, H. A. (2023). A new vision of photothermal therapy assisted with gold nanorods for the treatment of mammary cancers in adult female rats. Nanoscale Advances, 6(1), 170–187. https://doi.org/10.1039/d3na00595j
Glenn, A., & Armstrong, C. E. (2019). Physiology of red and white blood cells. Anaesthesia & Intensive Care Medicine, 20(3), 170–174. https://doi.org/10.1016/j.mpaic.2019.01.001
Gokul Raj, K., Chidambaram, R., Varunkumar, K., Ravikumar, V., & Pandi, M. (2015). Chemopreventive potential of fungal taxol against 7, 12-dimethylbenzaanthracene induced mammary gland carcinogenesis in Sprague Dawley rats. European Journal of Pharmacology, 767, 108-118. https://doi.org/10.1016/j.ejphar.2015.10.015
Gopalakrishnan, T., Ganapathy, S., Veeran, V., & Namasivayam, N. (2019). Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events. Biomedicine & Pharmacotherapy, 111, 178-187. https://doi.org/10.1016/j.biopha.2018.12.071
Guido, L. N., Fontelles, C. C., Rosim, M. P., Pires, V. C., Cozzolino, S. M. F., Castro, I. A., Bolaños-Jiménez, F., Barbisan, L. F., & Ong, T. P. (2016). Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenzaanthracene-induced mammary carcinogenesis in female rat offspring. International Journal of Cancer. Journal International Du Cancer, 139(8), 1873–1882. https://doi.org/10.1002/ijc.30223
Hamdy, S. M., Latif, A. K. M. A., Drees, E. A., & Soliman, S. M. (2012). Prevention of rat breast cancer by genistin and selenium. Toxicology and Industrial Health, 28(8), 746–757. https://doi.org/10.1177/0748233711422732
Hosny, S., Sahyon, H., Youssef, M., & Negm, A. (2021). Oleanolic acid suppressed DMBA-induced liver carcinogenesis through induction of mitochondrial-mediated apoptosis and autophagy. Nutrition and Cancer, 73(6), 968-982.
Karnam, K. C., Ellutla, M., Bodduluru, L. N., Kasala, E. R., Uppulapu, S. K., Kalyankumarraju, M., & Lahkar, M. (2017). Preventive effect of berberine against DMBA-induced breast cancer in female Sprague Dawley rats. Biomedecine & Pharmacotherapie, 92, 207–214. https://doi.org/10.1016/j.biopha.2017.05.069
Kieliszek, M., Bano, I., & Zare, H. (2022). A comprehensive review on selenium and its effects on human health and distribution in Middle Eastern countries. Biological Trace Element Research, 200(3), 971–987. https://doi.org/10.1007/s12011-021-02716-z
Kieliszek, M., Lipinski, B., & Błażejak, S. (2017). Application of sodium selenite in the prevention and treatment of cancers. Cells, 6(4), 39. https://doi.org/10.3390/cells6040039
Lakkis, N. A., Abdallah, R. M., Musharrafieh, U. M., Issa, H. G., & Osman, M. H. (2024). Epidemiology of breast, corpus uteri, and ovarian cancers in Lebanon with emphasis on breast cancer incidence trends and risk factors compared to regional and global rates. Cancer Control, 31. https://doi.org/10.1177/10732748241236266
Lippman, S. M., Klein, E. A., Goodman, P. J., Lucia, M. S., Thompson, I. M., Ford, L. G., Parnes, H. L., Minasian, L. M., Gaziano, J. M., Hartline, J. A., Parsons, J. K., Bearden, J. D., 3rd, Crawford, E. D., Goodman, G. E., Claudio, J., Winquist, E., Cook, E. D., Karp, D. D., Walther, P., … Coltman, C. A., Jr. (2009). Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The selenium and vitamin E cancer prevention trial (SELECT). JAMA: The Journal of the American Medical Association, 301(1), 39–51. https://doi.org/10.1001/jama.2008.864
Nilsonne, G., Olm, E., Szulkin, A., Mundt, F., Stein, A., Kocic, B., Rundlöf, A.-K., Fernandes, A. P., Björnstedt, M., & Dobra, K. (2009). Phenotype-dependent apoptosis signalling in mesothelioma cells after selenite exposure. Journal of Experimental & Clinical Cancer Research: CR, 28(1), 92. https://doi.org/10.1186/1756-9966-28-92
Pratama, D. A. O. A., Cahyati, A. N., Kustiati, U., Hardian, A. B., & Permata, F. S. (2023). Proteomics analysis of carcinogenesis in a rat model of mammary cancer induced by DMBA (7,12-dimethylbenzaanthracene). F1000Research, 12, 606. https://doi.org/10.12688/f1000research.132524.2
Rataan, A. O., Geary, S. M., Zakharia, Y., Rustum, Y. M., & Salem, A. K. (2022). Potential role of selenium in the treatment of cancer and viral infections. International Journal of Molecular Sciences, 23(4), 2215. https://doi.org/10.3390/ijms23042215
Russo, I. H., Russo, J. (1996). Mammary gland neoplasia in long-term rodent studies. Environmental health perspectives, 104(9), 938-967. https://doi.org/10.1289/ehp.96104938
Savitha, P. (n.d.). Role of Selenium. Psu.edu. Retrieved January 4, 2025, from https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=bf2dc62c1b63f6153c78a003a1c980fb0b8d558f
Selamoglu, Z., & Yilmaz, I. (2015). The Investigation of the Antioxidative Properties of the Synthetic Organoselenium Compounds in Liver Tissue of Rat with Histological and Biochemical Analyses.
Shankar, A., Wang, J. J., Rochtchina, E., Yu, M. C., Kefford, R., & Mitchell, P. (2006). Association between circulating white blood cell count and cancer mortality: a population-based cohort study: A population-based cohort study. Archives of Internal Medicine, 166(2), 188–194. https://doi.org/10.1001/archinte.166.2.188
Soukupová, K., & Rudolf, E. (2019). Suppression of proliferation and activation of cell death by sodium selenite involves mitochondria and lysosomes in chemoresistant bladder cancer cells. Journal of Trace Elements in Medicine and Biology: Organ of the Society for Minerals and Trace Elements (GMS), 52, 58–67. https://doi.org/10.1016/j.jtemb.2018.11.009
Szwiec, M., Marciniak, W., Derkacz, R., Huzarski, T., Gronwald, J., Cybulski, C., Dębniak, T., Jakubowska, A., Lener, M., Falco, M., Kładny, J., Baszuk, P., Duszyński, J., Kotsopoulos, J., Narod, S. A., & Lubiński, J. (2021). Serum selenium level predicts 10-year survival after breast cancer. Nutrients, 13(3), 953. https://doi.org/10.3390/nu13030953
Toyama, T., Kaneko, T., Arisawa, K., & Saito, Y. (2022). Metal-binding properties of selenoprotein P-its relation to structure and function. https://doi.org/10.11299/metallomicsresearch.MR202209
Tran, T. P. N., & Tran, T. T. N. (2024). Ethanol extract of black shallot (Allium ascalonicum Linnaeus) for breast cancer prevention: evidence from a DMBA-induced mouse model. Advances in Traditional Medicine. https://doi.org/10.1007/s13596-024-00781-y
Tu, K., Liu, K., Wang, Y., Jiang, Y., & Zhang, C. (2023). Association of dietary intake of Zinc and Selenium with breast cancer risk: A case-control study in Chinese women. Nutrients, 15(14), 3253. https://doi.org/10.3390/nu15143253
Wang, Z., & Zhang, X. (2017). Chemopreventive activity of honokiol against 7, 12 - dimethylbenzaanthracene-induced mammary cancer in female Sprague dawley rats. Frontiers in Pharmacology, 8, 320. https://doi.org/10.3389/fphar.2017.00320
Zeweil, M. M., Sadek, K. M., Abouzed, T. K., Wasef, L., Saleh, H., Albogami, S. M., ... & Batiha, G. E. S. (2023). Graviola Protects Against Hepatic Toxicity Associated with DMBA induced Breast Cancer via Restoration of Antioxidants and Attenuation of Inflammatory Pathways. Letters in Drug Design & Discovery, 20(10), 1593-1599. https://doi.org/10.2174/1570180819666220819142642
Zingué, S., Tchoupang, E. N., Madji, L. T., Pehuie Fomat, B. H., Mafogang, B., Njamen, D., & Mendimi, J. M. N. (2024). Ricinodendron heudelotii (Euphorbiaceae) seed oil prevents DMBA-induced breast cancer under menopause-like conditions in Wistar rats. Frontiers in Pharmacology, 15. https://doi.org/10.3389/fphar.2024.1389976

Authors

Nour EL-Houda Feriel Djebara
Adel Gouri
Houari Hemida
Chahinaise Zaoui
Bachir Benarba
bachirsb@yahoo.fr (Primary Contact)
Djebara , N. E.-H. F. ., Gouri, A., Hemida, H. ., Zaoui, C., & Benarba, B. . (2025). The Inhibitory Effect of Selenium Supplementation on Tumor Progression in a DMBA-Induced Breast Cancer Model in Wistar Rats. The North African Journal of Food and Nutrition Research, 9(20), 112–122. https://doi.org/10.51745/najfnr.9.20.112-122

Article Details

Received 2025-02-02
Accepted 2025-08-15
Published 2025-08-23