STUDY OF THE STRESS HORMONES EFFECT ON MICRONUTRIENT BALANCE IN EXPERIMENTS IN VITRO AND IN VIVO
DOI:
https://doi.org/10.15407/oncology.2026.01.030Keywords:
chronic stress, LNCaP and DU-145 cell lines, Guerin carcinoma, adrenaline, dexamethasone, copper, zinc, calciumAbstract
Summary. Aim: to investigate the effect of stress hormones on the metabolism of calcium, copper, and zinc in malignantly transformed cells (in vitro) and in animals with a model tumor process (in vivo). Objects and Methods: in vitro: determination of copper and zinc content in human prostate cancer cell lines LNCaP and DU-145 using the fluorescent probes Coppersensor 3 and ZnAF-2F, respectively, was performed on a Synergy HTX plate fluorometer. In vivo: epinephrine and dexamethasone (0.5 mg/kg) were administered for 12 days to Wistar rats – both intact and those with transplanted Guerin carcinoma. The trace element content in peripheral blood plasma was determined using an automatic biochemical analyzer with standard kits. Statistical processing of the results was carried out using the Statistica 12.0 software package. Results: in DU-145 cells under the influence of dexamethasone in vitro, there was an increase in Zn levels (by 15%), a slight decrease in Cu levels, and a reduction in the Cu/Zn ratio, which is considered a favorable prognostic factor. No significant effect of epinephrine on Zn and Cu content was observed. LNCaP cells were found to be resistant to the effects of both stress hormones. In the in vivo system, chronic stress led to significant disruption of mineral homeostasis. On the 7th day of the experiment, epinephrine and dexamethasone caused an increase in Cu and Ca levels and a decrease in Zn levels in the peripheral blood, which may be associated with changes in trace element transport. On the 14th and 21st days, the growth of Cu and Ca levels persisted under the influence of both hormones, accompanied by a simultaneous significant decrease in Zn content. Conclusion: stress hormones and the tumor process cause a significant imbalance of trace elements. In vitro, dexamethasone increases zinc levels in DU-145 cells, which may reduce tumor aggressiveness, while epinephrine shows no direct effect on metal content in the cells. In vivo, it was shown that chronic stress during tumor growth leads to increased levels of copper and calcium against a background of zinc deficiency.
References
Sandsveden M, Manjer J. Serum copper, zinc and copper/zinc ratio in relation to survival after breast cancer diagnosis: A prospective multicenter cohort study. Redox Biol 2023; 63: 102728. doi: 10.1016/j.redox.2023.102728.
Michalczyk K, Cymbaluk-Płoska A. The role of zinc and copper in gynecological malignancies. Nutrients 2020; 12 (12): 3732. https://doi.org/10.3390/nu12123732.
Clines GA, Guise TA. Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. Endocr Relat Cancer. 2005; 12 (3): 549–83. https://doi.org/10.1677/erc.1.00543.
Xiong K, Lu L, Ge P, et al. Calcium intake and risk of prostate cancer: A systematic review and dose-response meta-analysis of prospective cohort studies. J Trace Elem Med Biol 2025; 89: 127652. https://doi.org/10.1016/j.jtemb.2025.127652.
Monteith GR, Prevarskaya N, Roberts-Thomson SJ. The calcium-cancer signalling nexus. Nat Rev Cancer 2017; 17 (6): 367–80. https://doi.org/10.1038/nrc.2017.18.
Alharbi A, Zhang Y, Parrington J. Deciphering the role of Ca2+ signalling in cancer metastasis: From the bench to the bedside. Cancers (Basel) 2021; 13 (2): 179. https://doi.org/10.3390/cancers13020179.
Michalczyk K, Cymbaluk-Płoska A. The role of zinc and copper in gynecological malignancies. Nutrients 2020; 12 (12): 3732. https://doi.org/10.3390/nu12123732.
Tang X, Yan Z, Miao Y, et al. Copper in cancer: from limiting nutrient to therapeutic target. Front Oncol 2023; 13: 1209156. https://doi.org/10.3389/fonc.2023.1209156.
Zhang Y, Song M, Mucci LA, Giovannucci EL. Zinc supplement use and risk of aggressive prostate cancer: a 30-year follow-up study. Eur J Epidemiol 2022; 37 (12): 1251–60. https://doi.org/10.1007/s10654-022-00922-0.
Pieretti JC, Freire BM, Armentano GM, et al. Chronic exposure to nitric oxide sensitizes prostate cancer cells and improved ZnO/CisPt NPs cytotoxicity and selectivity. Int J Pharm 2023; 640: 122998. https://doi.org/10.1016/j.ijpharm.2023.122998.
Saleh SAK, Adly HM, Abdelkhaliq AA, Nassir AM. Serum levels of selenium, zinc, copper, manganese, and iron in prostate cancer patients. Curr Urol 2020; 14 (1): 44–9. https://doi.org/10.1159/000499261.
Cassera E, Ferrari E, Vignati DAL, Capucciati A. The interaction between metals and catecholamines: oxidative stress, DNA damage, and implications for human health. Brain Res Bull 2025; 226: 111366. https://doi.org/10.1016/j.brainresbull.2025.111366
Shkurashivska S, Ersteniuk H. The effect of adrenaline on the mineral and trace element status in rats. Open Life Sci 2019; 14: 158–64. https://doi.org/10.1515/biol-2019-0018.
Yamashita K, Ogihara T, Hayashi M, et al. Association between dexamethasone treatment and alterations in serum concentrations of trace metals. Pharmazie 2020; 75 (5): 218–22. https://doi.org/10.1691/ph.2020.034.
Xie L, Jiao Z, Zhang H, et al. Altered hippocampal GR/KCC2 signaling mediates susceptibility to convulsion in male offspring following dexamethasone exposure during pregnancy in rats. Toxicol Lett 2022; 364: 12–23. https://doi.org/10.1016/j.toxlet.2022.05.004.
Nobili F, Vignolini F, Figus E, Mengheri E. Treatment of rats with dexamethasone or thyroxine reverses zinc deficiency-induced intestinal damage. J Nutr 1997; 127 (9): 1807–13. https://doi.org/10.1093/jn/127.9.1807
