INFLUENCE OF EXOGENOUS LACTOFERRIN ON THE OXIDANT/ ANTIOXIDANT BALANCE AND MOLECULAR PROFILE OF HORMONE RECEPTOR-POSITIvE AND -NEGATIvE HUMAN BREAST CANCER CELLS IN VITRO

Abstract

Aim: To investigate the mechanisms of cytotoxic activity and pro-/antioxidant effect of lactoferrin on hormone receptor-positive and receptor-negative breast cancer cells in vitro. Materials and Methods: The study was performed on receptor-positive (MCF-7, T47D) and receptor-negative (MDA-MB-231, MDA-MB-468) human breast cancer cell lines. Immunocytochemical staining, flow cytometry, low-temperature electron paramagnetic resonance, and the Comet assay were used. Results: Upon treatment with lactoferrin, the increased levels of reactive oxygen species (ROS) (p < 0.05), NO generation rate by inducible NO-synthase (p < 0.05) and the level of “free” iron (p < 0.05) were observed. Moreover, the effects of lactoferrin were more pronounced in receptor-negative MDA-MB-231 and MDA-MB-468 cells. These changes resulted in increased expression of proapoptotic Bax protein (p < 0.05), reduced expression of the antiapoptotic Bcl-2 protein (p < 0.05) and level of not-oxidized mitochondrial cardiolipin (1.4–1.7-fold, p < 0.05). This, in turn, caused an increase in the percentage of apoptotic cells (by 14–24%, p < 0.05). Cytotoxic effects of lactoferrin were accompanied by an increase in the percentage of DNA in the comet tail and blocking cell cycle at G2/M phase, especially in receptor-negative cell lines. Conclusion: The study showed that exogenous lactoferrin causes a violation of an antioxidant balance by increasing the level of ROS, “free” iron and NO generation rate, resalting in the blocking of cell cycle at G2/M-phase and apoptosis of malignant cells.

Lactotransferrin Downregulation Drives the Metastatic Progression in Clear Cell Renal Cell Carcinoma

“…Furthermore, LTF inhibits osteosarcoma cell proliferation and migration by regulating LRP1 and NF-kB p65 [25]. LTF can induce apoptosis and cause cell cycle arrest in breast cancer [26]. In addition, LTF inhibits epithelial-to-mesenchymal transition (EMT) and induces mesenchymal-to-epithelial transition (MET) in oral squamous cell carcinoma [24].…”

Surface Enhanced Raman Spectroscopy of Lactoferrin Adsorbed on Silvered Porous Silicon Covered with Graphene

“…Organic dye Rhodamine 6G (R6G) and recombinant human lactoferrin [24,25] were used as analytes for the SERS measurements. The R6G dye (purchased from Sigma–Aldrich) and lactoferrin (received from the Department of Biochemistry of the Belarusian State University) had a 98% purity.…”

“…At the same time, the lactoferrin detection in its water solutions is very important, as they can be used in the therapy of different diseases including cancer. Recently, it was reported that exogenous lactoferrin can affect the rate of tumor cells growth [24]. In addition, it was shown that recombinant human lactoferrin has a beneficial effect on the intestinal microflora, ultrastructure of the liver and intestines, activated lipid metabolism and steroidogenesis [25].…”

Antitumor and Genotoxic Effects of Lactoferrin in Walker-256 Tumor-Bearing Rats

“…Comet assay. A standard classical method of alkaline gel electrophoresis of isolated cells was performed as described in [13]. Microscopic analysis was performed using a fluorescent microscope Axio Scope A.1 (Carl Zeiss, Germany).…”

“…An important feature of LF is its ability to bind to nucleic acids and to regulate cell cycle, proliferative activity of cells, and to affect the pro-and antioxidant balance in the cells. Human LF is a multifunctional glycoprotein that can inhibit cancer cells at G2/M phase [11,13].…”