ИСТИНА

Today one of the actual problem is organism «aging»: oxygenation of important cell components by reactive oxygen species (ROS) during misbalance between its production and cell reparation system. ROS are important for some signaling pathways and other essential processes in cells. However, increasing ROS concentration may lead to damage and degradation of DNA, lipids and proteins. Mitochondria are considered as the main producer of ROS during oxidative phosphorylation, active electron transport and reduction of the oxygen consumed by cells. Cancer cells have more ROS than normal ones due to the mitochondria functioning disruption [1]. In that way, the most interesting compounds are able to accumulate in mitochondria due to maximum influence on the ROS production. Recently the ability of synthetic dimeric bisbenzimidazoles with piperazine cycle in methylene linker, DBP(1-4), to interact not only with nucleus DNA but also with mitochondrial DNA was reported [2]. DBP(1-4) are effective inhibitors of DNA-C5-methyltransferases in cancer cells, however, it is still unknown how these compounds may influence on ROS production in different types of cells. The aim of the work was to study the influence of DBP(1-4) on oxidative stress in breast cancer cells MCF7 and embryonic lung fibroblasts F-977. The study included cultivating both cell types in the presence of different DBP(1-4) concentrations followed by evaluation of the ROS amount in cells. For this purpose the kinetics of reaction between cell-produced ROS and oxidation-sensitive 2’,7’-dichlorofluoresceine diacetate molecule (DCHF-DA) was studied. First data about the ability of DBP(1-4) to increase ROS production in breast cancer cells was obtained. There was practically no influence of DBP(1-4) on ROS production in normal cells. 1. Irani K., Zweier J.L., Goldschmidt-Clermont P.J. et al. Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts // Science. 1997, vol. 275, No.14, pp. 1649–1652. 2. Khrabrova D.A., Kvasha M.A., Veiko N.N., Kostuk S.V., Ershova E.S., Tashlitsky V.N., Zhuse A.L., Koval V.S., Ivanov A.A., Gromova E.S. Dimeric bisbenzimidazoles with piperaszine cycle in linker: influence on DNA-methylation in breast cancer cells // Advances in Molecular Oncology. 2016, vol.3, No.4, p.83. Supported by RFBR grant №16-04-01087.