ACTIVITY OF THREE DERIVATIVES ALKALOIDS TROPOLONE AND STUDYING OF SOME PARTIES OF THEIR MECHANISM OF ACTION
Actuality: The search and creation of new drug preparations with the antineoplastic action, possessing not only influence on some targets, but also overcoming resistance, was and remains actual in experimental and in clinical oncology. Research objective: Study of influence of new preparations К-50, К-60 and К-61 on proliferations and synthesis DNA/RNA of resistant cells S. cerevisiae, on synthesis DNA/RNA, an expression of genes the tumoral suppressor р53 and the MDR2 drug transporter on tumoral strain the Sarcoma 180 in comparison with effect etoposide. Material and methods: S. cerevisiae, animals transplantable tumor. Preparations DNA/RNA from cells S. cerevisiae and Sarcomas 180, have been isolation by protocol «DNA-sorb-B». Concentration DNA/RNA defined on adsorption at length of a wave of 260 nm on apparatus SF-26. Electrophoresis DNA/RNA analyzed in 1.5 % gel agarose during 4ч, 60В. Influence of preparations on MDR was spent on tumor cells Sarcoma 180. Expression level of MDR2 gene in tumor cells analyzed a method RTPCR. Results. Study of influence of preparations on synthesis DNA/RNA, topoisomerases activity, an expression of genes MDR2 and р53 in comparison with etoposide on a tumor the Sarcoma 180, it is established, that in a tumor cells preparations suppress synthesis DNA/RNA more considerably, lower level of an expression of gene MDR2 is observed (from 15 to 20%) in comparison with the increase of an expression of this gene under influence etoposide, the gene expression р53 considerably increases to 35-50 % (for etoposide to 20 %), that defines the big ability of new substances to induce апоптоз tumors. Conclusions. Influence of preparations on such tumoral targets as DNA and RNA, MDR2, р53 and topoisomerases I/II establishes the reasons of their powerful damage of tumoral cages.