Some microbial ribonucleases (RNases) demonstrate selective cytotoxic effect against a wide range of tumor cells. In this context combined use of cytotoxic RNases in complex therapy with other chemotherapeutic agents appears to be especially promising. In this study we have investigated the apoptosis-induced effect of Bacillus pumilus RNase (binase) in combination with known anti-tumor antibiotic bleomycin on human lung adenocarcinoma A549 cells. The combined effect of high concentrations of these agents did not have any mutual increase in their apoptosis-induced action, while a combination of non-apoptotic concentrations resulted in the increase of the proportion of apoptotic cells up to 22% as compared with individual effect of bleomycin (6%) and binase (12%) used separately. These results indicate that binase and bleomycin are effective in combination of their low concentrations and ineffective in combination of their high concentrations.
Riad ribonukleaz mikroorganizmov okazyvaet selektivnoe tsitotoksicheskoe deĭstvie v otnoshenii shirokogo spektra opukholevykh kletok. Osobenno perspektivnym predstavliaetsia ispol'zovanie tsitotoksichnykh RNKaz v sostave kompleksnoĭ terapii sovmestno s drugimi khimioterapevticheskimi sredstvami. V nastoiashcheĭ rabote issledovano indutsiruiushchee apoptoz deĭstvie RNKazy Bacillus pumilus (binazy) v sochetanii s izvestnym protivoopukholevym antibiotikom bleomitsinom na kletki adenokartsinomy legkogo cheloveka A549. Pri ispol'zovanii vysokikh kontsentratsiĭ issleduemykh veshchestv vzaimnoe usilenie indutsiruiushchego apoptoz deĭstviia preparatov ne obnaruzheno; sochetanie neapoptogennykh kontsentratsiĭ privelo k povysheniiu doli apoptoticheskikh kletok do 22% po sravneniiu s individual'nym deĭstviem bleomitsina (6%) i binazy (12%). Poluchennye dannye svidetel'stvuiut, chto binaza i bleomitsin éffektivny pri sochetanii v nizkikh i neéffektivny pri sochetaniiakh v vysokikh kontsentratsiiakh.
Keywords: Bacillus pumilus; antitumor activity; binase; bleomycin; cytotoxic ribonucleases; lung adenocarcinoma.