Abstract
Supplementation with the antioxidant selenium is frequently performed in breast cancer patients to protect the normal tissue from radiation-induced side effects. However, concerns exist whether selenium also protects tumor cells from radiation-induced cell kill and thereby reduces the efficacy of radiotherapy. In this work, the effect of selenium administration on the radiosensitivity of breast cancer cells was evaluated in vitro. Physiological relevant selenium concentrations (70 and 140 µg/l) did not affect DNA double-strand breaks (γH2AX foci) after 4-Gy X-ray irradiation. Also apoptosis (caspase 3/7) after irradiation with 10 Gy was not influenced by selenium treatment in MDA-MB-231 and MCF7 cells. Most importantly, selenium supplementation did not impair the clonogenic survival of the breast cancer cell lines after irradiation (0, 2, 4, 6, 8 Gy). The data suggest that physiological relevant selenium concentrations administered in combination with radiation therapy do not deteriorate the efficacy of radiotherapy in breast cancer patients. However, randomized clinical trials comparing the effectiveness of radiotherapy and the associated side effects in patients with and without selenium supplementation are recommended.
Similar content being viewed by others
References
Borek C (2004) Antioxidants and radiation therapy. J Nutr 134:3207S–3209S
Buntzel J et al (2010) Limited effects of selenium substitution in the prevention of radiation-associated toxicities. Results of a randomized study in head and neck cancer patients. Anticancer Res 30:1829–1832
Dorr W (2006) Effects of selenium on radiation responses of tumor cells and tissue. Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al] 182:693–695. https://doi.org/10.1007/s00066-006-1595-8
Eckers JC, Kalen AL, Xiao W, Sarsour EH, Goswami PC (2013) Selenoprotein P inhibits radiation-induced late reactive oxygen species accumulation and normal cell injury. Int J Radiat Oncol Biol Phys 87:619–625. https://doi.org/10.1016/j.ijrobp.2013.06.2063
Evans SO, Khairuddin PF, Jameson MB (2017) Optimising selenium for modulation of cancer treatments. Anticancer Res 37:6497–6509. https://doi.org/10.21873/anticanres.12106
Franca CA, Nogueira CR, Ramalho A, Carvalho AC, Vieira SL, Penna AB (2011) Serum levels of selenium in patients with breast cancer before and after treatment of external beam radiotherapy. Ann Oncol 22:1109–1112. https://doi.org/10.1093/annonc/mdq547
Grober U, Holzhauer P, Kisters K, Holick MF, Adamietz IA (2016) Micronutrients in oncological intervention. Nutrients 8:163. https://doi.org/10.3390/nu8030163
Husbeck B, Peehl DM, Knox SJ (2005) Redox modulation of human prostate carcinoma cells by selenite increases radiation-induced cell killing. Free Radic Biol Med 38:50–57. https://doi.org/10.1016/j.freeradbiomed.2004.09.022
Mayland C, Allen KR, Degg TJ, Bennet M (2004) Micronutrient concentrations in patients with malignant disease: effect of the inflammatory response. Ann Clin Biochem 41:138–141. https://doi.org/10.1258/000456304322880032
Micke O, Mucke R, Bruns F, Kisters K, Buntzel J (2007) Some clinical results on selenium in radiation oncology: letter by O. Micke, R. Mucke, F. Bruns, K. Kisters, J. Buntzel on W. Dorr: effects of selenium on radiation responses of tumor cells and tissue—in: Strahlenther Onkol 2006;182:693-5 (No. 12) (https://doi.org/10.1007/s00066-006-1595-8). Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al] 183:344–345. https://doi.org/10.1007/s00066-007-9595-x
Micke O, Schomburg L, Buentzel J, Kisters K, Muecke R (2009) Selenium in oncology: from chemistry to clinics. Molecules 14:3975–3988. https://doi.org/10.3390/molecules14103975
Muecke R et al (2010) Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology. Int J Radiat Oncol Biol Phys 78:828–835. https://doi.org/10.1016/j.ijrobp.2009.08.013
Muecke R et al (2014) Multicenter, phase III trial comparing selenium supplementation with observation in gynecologic radiation oncology: follow-up analysis of the survival data 6 years after cessation of randomization. Integr Cancer Ther 13:463–467. https://doi.org/10.1177/1534735414541963
Muecke R, Micke O, Schomburg L, Buentzel J, Kisters K, Adamietz IA, Akte (2018) Selenium in radiation oncology-15 years of experiences in Germany. Nutrients 10:10. https://doi.org/10.3390/nu10040483
Pakdaman A (1998) Symptomatic treatment of brain tumor patients with sodium selenite, oxygen, and other supportive measures. Biol Trace Elem Res 62:1–6. https://doi.org/10.1007/bf02820015
Pothier L, Lane WW, Bhargava A, Michielson C, Douglass HO Jr (1987) Plasma selenium levels in patients with advanced upper gastrointestinal cancer. Cancer 60:2251–2260
Puspitasari IM, Abdulah R, Yamazaki C, Kameo S, Nakano T, Koyama H (2014) Updates on clinical studies of selenium supplementation in radiotherapy. Radiat Oncol 9:125. https://doi.org/10.1186/1748-717X-9-125
Puspitasari IM, Yamazaki C, Abdulah R, Putri M, Kameo S, Nakano T, Koyama H (2017) Protective effects of sodium selenite supplementation against irradiation-induced damage in non-cancerous human esophageal cells. Oncol Lett 13:449–454. https://doi.org/10.3892/ol.2016.5434
Rayman MP (2005) Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc 64:527–542
Rodemann HP, Hehr T, Bamberg M (1999) Relevance of the radioprotective effect of sodium selenite. Medizinische Klinik 94(Suppl 3):39–41
Schilling D, Bayer C, Li W, Molls M, Vaupel P, Multhoff G (2012) Radiosensitization of normoxic and hypoxic h1339 lung tumor cells by heat shock protein 90 inhibition is independent of hypoxia inducible factor-1alpha. PLoS One 7:e31110. https://doi.org/10.1371/journal.pone.0031110
Schilling D, Kuhnel A, Konrad S, Tetzlaff F, Bayer C, Yaglom J, Multhoff G (2015) Sensitizing tumor cells to radiation by targeting the heat shock response. Cancer Lett 360:294–301. https://doi.org/10.1016/j.canlet.2015.02.033
Schleicher UM, Lopez Cotarelo C, Andreopoulos D, Handt S, Ammon J (1999) Radioprotection of human endothelial cells by sodium selenite. Medizinische Klinik 94(Suppl 3):35–38
Schueller P, Puettmann S, Micke O, Senner V, Schaefer U, Willich N (2004) Selenium influences the radiation sensitivity of C6 rat glioma cells. Anticancer Res 24:2913–2917
Shin SH, Yoon MJ, Kim M, Kim JI, Lee SJ, Lee YS, Bae S (2007) Enhanced lung cancer cell killing by the combination of selenium and ionizing radiation. Oncol Rep 17:209–216
Tian J, Ning S, Knox SJ (2010) Sodium selenite radiosensitizes hormone-refractory prostate cancer xenograft tumors but not intestinal crypt cells in vivo. Int J Radiat Oncol Biol Phys 78:230–236. https://doi.org/10.1016/j.ijrobp.2010.03.006
Zeng YC et al (2012) Serum levels of selenium in patients with brain metastases from non-small cell lung cancer before and after radiotherapy. Cancer Radiother 16:179–182. https://doi.org/10.1016/j.canrad.2011.11.003
Acknowledgements
The authors thank Andrea Mair and Marlon Stein for excellent technical assistance.
Funding
This research received no external funding.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Schilling, D., Herold, B., Combs, S.E. et al. Selenium does not affect radiosensitivity of breast cancer cell lines. Radiat Environ Biophys 58, 433–438 (2019). https://doi.org/10.1007/s00411-019-00801-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00411-019-00801-5