Anticancer effects of sodium selenate in human neuroblastoma, breast cancer, and melanoma cells

Abstract

Sodium selenate (Na2SeO4) is one of the oxidized inorganic forms of selenium. Effects on cytotoxicity, total antioxidant level, total oxidant level, oxidative stress, and genotoxicity status and its anticancer effect on SH-SY5Y human neuroblastoma, MCF-7 human breast cancer, and 451Lu human melanoma cells were investigated in this study. Sodium selenate exhibited a highly cytotoxic effect at all concentrations (0.078125 - 10 mg/mL) against SH-SY5Y, MCF-7, and 451Lu cancer cell lines. In addition, sodium selenate reduced the total antioxidant levels, increased the total oxidant levels (except for SH-SY5Y), and induced oxidative stress significantly in SH-SY5Y, MCF-7, and 451Lu cells. However, in agarose gel electrophoresis images, it was observed that sodium selenate did not have any genotoxic effect on SH-SY5Y, MCF-7, and 451Lu cancer cells. Sodium selenate can be used in cancer treatment because of its antioxidant, as well as pro-oxidant and anticancer properties, which depend on the concentrations used.

Keywords

• Sodium selenate
• Oxidative stress
• Anticancer
• SH-SY5Y cells
• MCF-7 cells
• 451Lu cells

References

1. Arnér, E.S. (2009). Focus on mammalian thioredoxin reductases important selenoproteins with versatile functions. Biochimica et Biophysica Acta (BBA)-General Subjects, 1790(6), 495-526.
2. Birben, E., Sahiner, U.M., Sackesen, C., Erzurum, S., & Kalayci, O. (2012). Oxidative stress and antioxidant defense. World Allergy Organization Journal, 5, 9-19.
3. Bray, F., Laversanne, M., Sung, H., Ferlay, J., Siegel, R.L., Soerjomataram, I., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229-263. https://doi.org/https://doi.org/10.3322/caac.21834
4. Brigelius-Flohé, R., & Maiorino, M. (2013). Glutathione peroxidases. Biochimica et Biophysica Acta (BBA)-General Subjects, 1830(5), 3289-3303.
5. Burk, R.F., & Hill, K.E. (2015). Regulation of selenium metabolism and transport. Annual Review of Nutrition, 35(1), 109-134.
6. Cao, S., Jin, H., Wang, C., Cao, Y., Fan, R., & Zhang, J. (2019). Sodium selenate induces apoptosis in human hepatocellular carcinoma cells by upregulating PTEN expression. Journal of Cellular Biochemistry, 120(9), 15264-15273.
7. Chen, Z., Lai, H., Hou, L., & Chen, T. (2019). Rational design and action mechanisms of chemically innovative organoselenium in cancer therapy. Chemical Communications, 56(2), 179-196. https://doi.org/10.1039/c9cc07683b
8. Choi, A.-R., Jo, M.J., Jung, M.-J., Kim, H.S., & Yoon, S. (2015). Selenate specifically sensitizes drug-resistant cancer cells by increasing apoptosis via G2 phase cell cycle arrest without P-GP inhibition. European Journal of Pharmacology, 764, 63-69.

9. Corcoran, N., Hovens, C., Michael, M., Rosenthal, M., & Costello, A. (2010). Open-label, phase I dose-escalation study of sodium selenate, a novel activator of PP2A, in patients with castration-resistant prostate cancer. British Journal of Cancer,103(4), 462-468.
10. da Costa, N.S., Lima, L.S., Oliveira, F.A.M., Galiciolli, M.E.A., Manzano, M.I., Garlet, Q.I., ... Oliveira, C.S. (2023). Antiproliferative Effect of Inorganic and Organic Selenium Compounds in Breast Cell Lines. Biomedicines, 11(5), 1346.
11. Foster, L.H., & Sumar, S. (1997). Selenium in health and disease: a review. Critical Reviews in Food Science and Nutrition, 37(3), 211-228. https://doi.org/10.1080/10408399709527773
12. Gandin, V., Khalkar, P., Braude, J., & Fernandes, A.P. (2018). Organic selenium compounds as potential chemotherapeutic agents for improved cancer treatment. Free Radical Biology and Medicine, 127, 80 97. https://doi.org/https://doi.org/10.1016/j.freeradbiomed.2018.05.001
13. Gorrini, C., Harris, I.S., & Mak, T.W. (2013). Modulation of oxidative stress as an anticancer strategy. Nature Reviews Drug Discovery, 12(12), 931-947. https://doi.org/10.1038/nrd4002
14. Jiang, C., Wang, Z., Ganther, H., & Lu, J. (2001). Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells. Cancer Research, 61(7), 3062-3070.
15. Khalkar, P., Díaz-Argelich, N., Antonio Palop, J., Sanmartín, C., & Fernandes, A.P. (2018). Novel Methylselenoesters Induce Programed Cell Death via Entosis in Pancreatic Cancer Cells. International Journal of Molecular Sciences, 19(10), 2849. https://www.mdpi.com/1422-0067/19/10/2849
16. Köhrle, J. (2000). The selenoenzyme family of deiodinase isozymes controls local thyroid hormone availability. Reviews in Endocrine and Metabolic Disorders, 1, 49-58.
17. Misra, S., Boylan, M., Selvam, A., Spallholz, J.E., & Björnstedt, M. (2015). Redox-active selenium compounds from toxicity and cell death to cancer treatment. Nutrients, 7(5), 3536-3556. https://doi.org/10.3390/nu7053536
18. Mou, Y., Wang, J., Wu, J., He, D., Zhang, C., Duan, C., & Li, B. (2019). Ferroptosis, a new form of cell death: opportunities and challenges in cancer. Journal of Hematology & Oncology, 12, 1-16.
19. Preiser, J.C. (2012). Oxidative stress. Journal of Parenteral and Enteral Nutrition, 36(2), 147-154.
20. Radomska, D., Czarnomysy, R., Radomski, D., & Bielawski, K. (2021). Selenium compounds as novel potential anticancer agents. International Journal of Molecular Sciences, 22(3), 1009.
21. Rayman, M.P. (2012). Selenium and human health. The Lancet, 379(9822), 1256-1268.
22. Rikiishi, H. (2007). Apoptotic cellular events for selenium compounds involved in cancer prevention. Journal of Bioenergetics and Biomembranes, 39, 91-98.
23. Sanmartín, C., Plano, D., Sharma, A.K., & Palop, J.A. (2012). Selenium compounds, apoptosis and other types of cell death: An overview for cancer therapy. International Journal of Molecular Sciences, 13(8), 9649-9672. https://www.mdpi.com/1422-0067/13/8/9649
24. Sinha, R., & El-Bayoumy, K. (2004). Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy by selenium compounds. Current Cancer Drug Targets, 4(1), 13-28. https://doi.org/10.2174/1568009043481614
25. Subburayan, K., Thayyullathil, F., Pallichankandy, S., Cheratta, A.R., & Galadari, S. (2020). Superoxide-mediated ferroptosis in human cancer cells induced by sodium selenite. Translational Oncology, 13(11), 100843. https://doi.org/10.1016/j.tranon.2020.100843
26. Tsukamoto, T., Hama, S., Kogure, K., & Tsuchiya, H. (2013). Selenate induces epithelial mesenchymal transition in a colorectal carcinoma cell line by AKT activation. Experimental Cell Research, 319(13), 1913-1921.
27. Ursini, F., & Maiorino, M. (2020). Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radical Biology and Medicine, 152, 175 185. https://doi.org/10.1016/j.freeradbiomed.2020.02.027
28. Yang, L., Cai, Y.-S., Xu, K., Zhu, J.-L., Li, Y.-B., Wu, X.-Q., ... Xu, P. (2018). Sodium selenite induces apoptosis and inhibits autophagy in human synovial sarcoma cell line SW982 in vitro. Molecular Medicine Reports, 17(5), 6560-6568.
29. Zeng, H., Briske-Anderson, M., Wu, M., & Moyer, M.P. (2012). Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation. Nutrition and Cancer, 64(1), 128-135. https://doi.org/10.1080/01635581.2012.630555
30. Zhang, Y., Cartland, S.P., Henriquez, R., Patel, S., Gammelgaard, B., Flouda, K., ... Rayner, B.S. (2020). Selenomethionine supplementation reduces lesion burden, improves vessel function and modulates the inflammatory response within the setting of atherosclerosis. Redox Biology, 29, 101409. https://doi.org/https://doi.org/10.1016/j.redox.2019.101409