Influence of ferromagnetic nanocomposite (Ferroplat) on human breast cancer cells of different malignancy degrees: pro/antioxidant balance and energy metabolism
Keywords:breast cancer, cardiolipin, energy metabolism, Ferroplat, glycolysis, malignancy degree, mitochondria, pro/antioxidant balance, reactive oxygen species, resistance
Summary. Aim: To study the effect of Ferroplat (FrP) on the indexes of pro/antioxidant balance and energy metabolism in breast cancer cells of different malignancy degree and different sensitivity to drug therapy. Materials and Methods: The study was carried out on breast cancer cells of low (T47D, MCF-7) and high malignancy degree (MCF-7/DDP (cisplatin-resistant), MDA-MB-231, MDA-MB-468) using cell culture techniques, immunocytochemical, biochemical, biophysical methods, flow cytometry and polarography. Results: We established that the addition of FrP to the culture medium reduces the activity of glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD) and the level of non-protein thiols by 32–41% (p < 0.05). At the same time, there was an increase of the total level of ROS and the rate of NO generation by inducible NO synthase by 1.7–2.5 times (p < 0.05). This testifies that FrP disturbs the antioxidant balance in cells, resulting in their death. Also, the use of FrP led to a decrease in the rate of oxygen absorption in MCF-7 and T47D cells by 26% and 25%, respectively (p < 0.05). In cells of high malignancy degree this index decreased by 38–40% under the influence of FrP. Incubation of MCF-7 and T47D cells with the indicated agent also reduced the content of phospholipid cardiolipin by 15–16% (p < 0.05), and in MDA-MB-231, MCF-7/DDP, MDA-MB-468 cells — by 29%, 30% and 32%, respectively. In addition, the effect of FrP caused a decrease in the levels of Mg2+ and lactate in MCF-7 and T47D cells by 21–29% and 14–24%, respectively, whereas in MDA-MB-231, MDA-MB-468, MCF-7/DDP cells — by 34–38% and 32–35%, respectively. In this case, the agent raised the level of glucose in the cells of low malignancy degree by 20–23% (p < 0.05), and in the cells of high malignancy degree and with the phenotype of drug resistance — by 31–36%. However, the nanocomposite did not affect the activity of lactate dehydrogenase in all studied breast cancer cells. Conclusion: The study has shown that FrP has an effect on the pro/antioxidant balance and energy metabolism of cancer cells. In addition, the denoted effect of FrP was more pronounced in the breast cancer cells with a high malignancy degree and the phenotype of drug resistance.
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