The influence of lactoferrin on elemental homeostasis and activity of metal-containing enzymes in rats with Walker-256 carcinosarcoma


  • Yu.V. Lozovska R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • I.M. Andrusishina SI “Yu.I. Kundiev Institute of Occupational Health”, NAMS of Ukraine, Kyiv 01033, Ukraine
  • N.Yu. Lukianova R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • A.P. Burlaka R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • L.A. Naleskina R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • I.N. Todor R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • V.F. Chekhun R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology



ceruloplasmin, essential elements, lactoferrin, myeloperoxidase, transferrin, Walker-256 carcinosarcoma


Summary. Aim: To investigate the content of essential elements (EE): copper, zinc, magnesium, iron and calcium and the evaluation of the activity of metal-containing enzymes — ceruloplasmin (CP), myeloperoxidase (MPO) and the content of transferrin (TF) in blood plasma (BP) and tumor tissue (TT) of animals with Walker-256 carcinosarcoma treated with lactoferrin (LF). Materials and Methods: The study of the EE content and the activity of the abovementioned enzymes was carried out on rats with Walker-256 carcinosarcoma treated with LF at the doses of 1 and 10 mg/kg of body weight. The quantitative content of EE in BP and TT of animals was determined using the inductively coupled plasma atomic emission spectroscopy (ICP-AES). Determination of CP activity, content of TF and hemochromes was performed using the method of electron paramagnetic resonance (EPR), and MPO — by unified biochemical method. Results: The introduction of LF at the doses of 1 and 10 mg/kg resulted in a decrease in the ratio of Cu/Zn in BP and even more expressed decrease of Ca/Mg ratio in TT. Administration of LF, especially at a dose of 10 mg/kg, affected the increase in CP and MPO activity in BP. It has been shown that administration of LF at a dose of 10 mg/kg led to an increase in oxidative products of destruction of the hemoglobin-hemochrom system in the TT, against the background of lowering the TF content. Conclusions: The administration of LF, especially at a dose of 10 mg/kg, led to metabolic alterations associated with inhibition of the tumor process. The detected modulating effect of LF on the content of the EE and the activity of the CP and MPO may be a basis for correction of the elemental balance in carcinogenesis.


Duffy MJ, Harbeck N, Nap M, et al. Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer 2017; 75: 284–8.

Tao Z, Shi A, Lu C, et al. Breast cancer: epidemiology and etiology. Cell Biochem Biophys 2015; 72: 333–8.

Tillashaykhov MN, Khudaykulov AT, Danilova EA, et al. Study of trace elements status of breast cancer patients. Оncology 2017; 19: 25–8 (in Ukrainian).

Turski ML, Thiele DJ. New roles for copper metabolism in cell proliferation, signaling, and disease. J Biol Chem 2009; 284: 717–21.

Formigari A, Gregianin E, Irato P. The effect of zinc and the role of p53 in copper-induced cellular stress responses. J Appl Toxicol 2013; 33: 527–36.

Yu Y, Kovacevic Z, Richardson R. Tuning cell cycle regulation with an iron key. Cell Cycle 2007; 6: 1982–94.

Hentze MW, Muckenthaler MU, Galy B, et al. Two to tango: regulation of mammalian iron metabolism. Cell 2010; 142: 24–38.

Ishida S, Andreux P, Poitry-Yamate C, et al. Bioavailable copper modulates oxidative phosphorylation and growth of tumors. Proc Natl Acad Sci USA 2013; 110: 19507–12.

Wolf FI, Cittadini AR, Maier JA. Magnesium and tumors: Ally or foe? Cancer Treat Rev 2009; 35: 378–82.

Beguin Y, Aapro M, Ludwig H, et al. Epidemiological and nonclinical studies investigating effect of iron in carcinogenesis — a critical review. Crit Rev Oncol Hematol 2014; 89: 1–15.

Lansu K, Gentile S. Potassium channel activation inhibits proliferation of breast cancer cells by activating a senescence program. Cell Death Dis 2013; 4: e652.

Rigiracciolo DC, Scarpelli A, Lappano R, et al. Copper activates HIF-1α/GPER/VEGF signalling in cancer cells. Oncotarget 2015; 6: 34158–77.

Qian Y, Yin C, ChenY, et al. Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element. Cell Signal 2015; 27: 934–42.

Mendes PMV, Bezerra DLC, Dos Santos LR, et al. Magnesium in breast cancer: what is its influence on the progression of this disease? Biol Trace Elem Res 2018; 184: 334–9.

Sahmoun AE, Singh BB. Does a higher ratio of serum calcium to magnesium increase the risk for postmenopausal breast cancer? Med Hypotheses 2010; 75: 315–8.

Lee CM, Lo HW, Shao RP, et al. Selective activation of ceruloplasmin promoter in ovarian tumors: potential use for gene therapy. Cancer Res 2004; 64: 1788–93.

Pradhan A, Herrero-de-Dios C, Belmonte R, et al. Elevated catalase expression in a fungal pathogen is a double-edged sword of iron. PLoS Pathog 2017; 13: e1006405.

Zabłocka-Słowińska K, Płaczkowska S, Prescha A, et al. Serum and whole blood Zn, Cu and Mn profiles and their relation to redox status in lung cancer patients. J Trace Elem Med Biol 2018; 45: 78–84.

Antoniades V, Sioga A, Dietrich EM, at al. Is copper chelation an effective anti-angiogenic strategy for cancer treatment? Med Hypotheses 2013; 81: 1159–63.

Lane DJ, Mills TM, Shafie NH, et al. Expanding horizons in iron chelation and the treatment of cancer: Role of iron in the regulation of ER stress and the epithelial-mesenchymal transition. Biochim Biophys Acta 2014; 1845: 166–81.

Blockhuys S, Wittung-Stafshede P. Roles of copper-binding proteins in breast cancer. Int J Mol Sci 2017; 18: e871.

Goodman VL, Brewer GJ, Merajver SD. Copper deficiency as an anti-cancer strategy. Endocr Relat Cancer 2004; 11: 255–63.

Tury S, Vacher S, Assayag F, Bonin F, et al. The iron chelator deferasirox synergises with chemotherapy to treat triple-negative breast cancers. J Pathol 2018; 246: 103–14.

Chekhun VF, Storchay DM, Shvets YV, et al. Cytotoxic effects of exogenous lactoferrin on breast cancer cells with different degree of malignancy in vitro. Exp Oncol 2016; 38: 131.

Chekhun VF, Storchay DM, Todor IN, et al. Antitumor and genotoxic effects of lactoferrin in Walker-256 tumor-bearing rats. Exp Oncol 2018; 40: 200–4.

Fernández-Menéndez S, Fernández-Sánchez ML, González-Iglesias H, et al. Iron bioavailability from supplemented formula milk: effect of lactoferrin addition. Eur J Nutr 2017; 56: 2611–20.

Baker EN, Anderson BF, Baker HM, et al. Metal and anion bindings sites in lactoferrin and related proteins. Pure Appl Chem 1990; 62: 1067–70.

Sokolov AV, Zakahrova ET, Kostevich VA, et аl. Lactoferrin, myeloperoxidase, and ceruloplasmin: complementary gearwheels cranking physiological and pathological processes. BioMetals 2014; 27: 815–28.

Recalcati S, Minotti G, Cao G. Iron regulatory proteins: from molecular mechanisms to drug development. Antioxid Redox Signal 2010; 13: 1593–616.

Terpinskaya TI, Pavlovets LV. The effect of human lactoferrin obtained from the milk of transgenic goats on the growth of transplantable tumors in mice Healthcare. Minsk (Belarus) 2013; 2: 33–7.

Zalutsky IW, Lukashevich VS, Lukyanova NYu, et al. Effect of exogenous lactoferrin on the development of an experimental model of breast carcinoma. Rep NAS of Belarus 2017; 61: 103–8.

Andrusishina IM, Lampeka OG, Golub IO, et al. Estimation of the damage to the professional community in professional contingents for the additional method of atomic energy spectroscopy from inductively coupled plasma. UkrTsNMI and the PCR of the registry No. 72-K: Avitsen 2014: 60 (in Ukrainian).

Burlaka AP, Sydorik EP. Radical forms of acid and nitrogen oxides during the fat process. K: Naukova Dumka, 2006. 228 p. (in Ukrainian).

Schierwagen C., Bylund-Fellenius AC, Lundberg C. Improved method for quantification of tissue PMN accumulation measured by myeloperoxidase activity. J Pharmacol Methods 1990; 23: 179–86.

Masson PL, Heremans JF. Metal-combining properties of human lactoferrin (red milk protein). The involvement of bicarbonate in the reaction. Eur J Biochem 1968; 6: 579–84.

Chekhun VF, Lozovska YuV, Burlaka AP, et аl. Peculiarities of antioxidant system and iron metabolism in organism during development of tumor resistance to cisplatin. Exp Oncol 2014; 36: 196–201.

Rodrigues GP, Cozzolino SMF, Marreiro DDN, et al. Mineral status and superoxide dismutase enzyme activity in Alzheimer’s disease. J Trace Elem Med Biol 2017; 44: 83–7.

Krzyminiewski R, Dobosz B, Kubiak T. The influence of radiotherapy on ceruloplasmin and transferrin in whole blood of breast cancer patients. Radiat Environ Biophys 2017; 56: 345–52.

Kim SW, Lee YJ, Chung JW, et al. A higher ratio of serum calcium to magnesium is associated with aggressive clinicopathological characteristics in the patients who underwent radical prostatectomy. Korean J Urol Oncol 2018; 16: 25–31.

Ambrosone СВ, Barlow WE, Reynolds W. Myeloperoxidase genotypes and enhanced efficacy of chemotherapy for early-stage breast cancer in SWOG-8897. J Clin Oncol 2009; 27: 4973–9.

Rymaszewski AL, Tate E, Yimbesalu JP. The role of neutrophil myeloperoxidase in models of lung tumor development. Cancers (Basel) 2014; 6: 1111–27.

Castillo-Tong DC, Pils D, Heinze G, et al. Association of myeloperoxidase with ovarian cancer. Tumour Biol 2014; 1: 141–8.

Däster S, Eppenberger-Castori S, Hir C, et al. Absence of myeloperoxidase and CD8 positive cells in colorectal cancer infiltrates identifies patients with severe prognosis. Oncoimmunology 2015; 4: e1050574.

Maneva A, Taleva B, Manevab L. Lactoferrin-protector against oxidative stress and regulator of glycolysis in human erythrocytes. Z Naturforsch 2003; 58: 256–62.

Vercellotti GM, van Asbeck BS, Jacob HS. Oxygen radical-induced erythrocyte hemolysis by neutrophils critical role of iron and lactoferrin. J Clin Inv 1985; 76: 956–62.




How to Cite

Lozovska, Y., Andrusishina, I., Lukianova, N., Burlaka, A., Naleskina, L., Todor, I., & Chekhun, V. (2023). The influence of lactoferrin on elemental homeostasis and activity of metal-containing enzymes in rats with Walker-256 carcinosarcoma. Experimental Oncology, 41(1), 20–25.



Original contributions

Most read articles by the same author(s)

<< < 1 2 3