Influence of exogenous lactoferrin on the oxidant/ antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro

• Дата: 2017
• Автори: Zalutski, I.V., Lukianova, N.Y., Storchai, D.M., Burlaka, A.P., Shvets, Y.V., Borikun, T.V., Todor, I.M., Lukashevich, V.S., Rudnichenko, Y.A., Chekhun, V.F.
• Формат: Стаття
• Мова: English
• Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2017
• Назва видання: Experimental Oncology
• Теми: Original contributions
• Онлайн доступ: http://dspace.nbuv.gov.ua/handle/123456789/137977
• Назва журналу: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Цитувати: Influence of exogenous lactoferrin on the oxidant/ antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro / I.V. Zalutski, N.Y. Lukianova, D.M. Storchai, A.P. Burlaka, Y.V. Shvets, T.V. Borikun, I.M. Todor, V.S. Lukashevich, Y.A. Rudnichenko, V.F. Chekhun // Experimental Oncology. — 2017 — Т. 39, № 2. — С. 106–111. — Бібліогр.: 21 назв. — англ.

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.