Autor: |
Vasilieva SV; N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 Kosygin Street, Moscow, Russia, 119334. svasilieva@chph.ras.ru., Petrishcheva MS; N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 4 Kosygin Street, Moscow, Russia, 119334., Yashkina EI; Federal State Institution A.I. Burnazyan Federal Medical and Biophysical Center, 46 Zhivopisnaya Street, Moscow, Russia, 123182., Osipov AN; N.N. Semyonov Institute of Chemical Physics, Russian Academy of Sciences, 4a Kosygin Street, Moscow, Russia, 119334. |
Abstrakt: |
Signaling and physiological activities of the crystalline tetranitrosyl iron complex with thiosulfate-a NO-donor (TNICthio) were first studied on human cells in conditions of mono and combined application of H 2 S and antioxidants. Comparative studies were performed on three cell lines: normal and leukemic T lymphocytes (Jurkat cells) and breast cancer MCF-7 cells (human breast adenocarcinoma). Also established was a high biological activity of TNICthio, as well as correlation between the levels of reactive oxygen species generation, the formation of double-strand breaks (DSB) in DNA and cell proliferation. The amount of DNA DSB repair in normal lymphocytes was tenfold higher than in leukemic cells. Inorganic H 2 S donor sodium hydrosulfide (NaHS) had insignificant effects on the production of reactive oxygen species and generation of DNA DSB in the cells of all the lines under study. However, H 2 S increased the tolerance of cells to the stress response after combined cell treatment with NO + H 2 S. 0.5 mM NO-donor and 0.1 mM antitumor antibiotic doxorubicin were equally effective generators of reactive oxygen species in MCF-7 cells; however, antiproliferative activity of the NO-donor, in this case, proved to be twice higher. The results obtained in this work may be promising for the prediction of pro- and antioxidant properties of the new NO and H 2 S donating compounds, as well as for the development of methods for complex anticancer therapy. |