INDUCTION OF APOPTOSIS IN CULTURED CHINESE HAMSTER OVARY CELLS BY UKRAIN AND ITS SYNERGISTIC ACTION WITH ETOPOSIDE

KUROCHKIN S.N.,¹ KOLOBKOV S.L.,² VOTRIN I.L.,^†3 VOLTCHEK I.V.⁴

1) Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
2) Center of Medical Biotechnology, Ministry of Health, Moscow, Russia.
3) Institute of Biological and Medical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia.
4) Terra Medica, St. Petersburg, Russia.

Address for correspondence: I.V. Voltchek, Terra Medica, Zanevsky pr., 1, of. 255, St. Petersburg, 195196, Russia.

Summary: The induction of apoptosis by Ukrain, a novel antitumor drug, was studied in Chinese hamster ovary (CHO) cells bearing multiple copies of recombinant human erythropoietin gene incorporated into their genome (cell lines CHO-k38 and -k38/12). Ukrain was found to be capable of the in vitro induction of apoptosis in the cell lines studied. The effect was less expressed in cells with type I multiple drug resistance (k38/12). Ukrain acted synergistically with etoposide, i.e., the combined effect of both agents was evident at significantly reduced concentrations. This suggests that pharmacological compositions of the drugs may reduce the effective doses used in chemotherapy and thus significantly diminish its toxic side effects. Ukrain was found to exert an unusual effect, manifested as the inhibition of protein secretion by target cells. This phenomenon may be used for the express determination of cell sensitivity to colchicine-like cytostatics, including Ukrain.