Signaling and physiological activity of the NO-donating agent TNICthio in human blood lymphocytes, Jurkat and MCF7 cell lines.

Abstract

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 H2S 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 H2S 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, H2S increased the tolerance of cells to the stress response after combined cell treatment with NO + H2S. 0.5mM NO-donor and 0.1mM 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 H2S donating compounds, as well as for the development of methods for complex anticancer therapy.