A multi-centre study on the role of the thioredoxin system in breast cancer cell proliferation

Abstract

Redox proteins (thioredoxin, glutaredoxin) are key macromolecules capable of modulating intracellular processes. This determines research choices in the field of redox-dependent cell proliferation management. The study of the molecular mechanisms of the onset, development and progression of malignant neoplasms underlies the search for tumor-associated markers and potential targets for personalized antitumor therapy.Purpose. To establish the role of the “thioredoxin – thioredoxin-reductase” system in the impaired proliferation of mammary adenocarcinoma cells under the action of the cyclin-dependent protein kinase roskovitin blocker.Materials and methods. The study was carried out using the culture of mammary adenocarcinoma cells of the MCF-7 line incubated in the presence and absence of roskovitin at a final concentration of 20 μM for 18 h. The intracellular content of thioredoxin and protein regulators of proliferation (cyclin E and cyclin-dependent protein kinase 2) were determined by Western blotting technique, the expression level of thioredoxin mRNA was determined by real-time polymerase chain reaction and the activity of thioredoxin-reductase was measured by a spectrophotometric method.Results. It was established that the decrease in proliferative activity of MCF-7 tumor cells incubated in the presence of roskovitin was accompanied by a decrease in the content of cyclin E and cyclin-dependent kinase on the background of a decrease in the expression level of thioredoxin mRNA and an increase in the activity of thioredoxin-reductase.Conclusion. The involvement of the components of the thioredoxin system (thioredoxin, thioredoxinreductase) in disrupting the proliferation of MCF-7 tumor cells was detected under the action of the cyclindependent protein kinases of roskovitin.

Keywords

• thioredoxin
• breast adenocarcinoma
• redox regulation
• proliferation