The subject of the research was to evaluate the mechanism of the anti-cancer activity of metformin (MET) in an experimental model of breast cancer. MET, a drug used in the treatment of type II diabetes, shows not only the ability to inhibit glucose production, but also inhibits cellular respiration inducing cancer cell death through apoptosis. In the course of many years of research, evidence has been presented of the association of the anti-cancer effect of MET with glucose metabolism, the Krebs cycle, the urea cycle and amino acid metabolism. A comprehensive metabolomic analysis has shown that MET under certain metabolic conditions inhibits glucose "burning" and energy metabolism, inducing apoptosis. An important discovery in the framework of the conducted research was the demonstration that an effect similar to MET can be obtained by knockout (CRISPR-Cas-9 technology) of proline dehydrogenase/proline oxidase (PRODH/POX), a mitochondrial enzyme involved in the energy metabolism of the cell. The results of these studies indicate a key role of this enzyme in the mechanism of the anti-cancer activity of MET, indicating that PRODH/POX may represent a new target for experimental cancer pharmacotherapy. Planned in vivo studies on various experimental cancer models may provide knowledge about the effectiveness of the PRODH/POX knockout in inducing cancer cell death.
This work was supported by the National Science Centre (number of project: 2017/25/B/NZ7/02183). This research was conducted within the project which has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 754432 and the Polish Ministry of Science and Higher Education, from financial resources for science in 2018-2023 granted for the implementation of an international co-financed project.
