Effects of Ukrain on the activities of DNA-nicking enzymes.

We studied the effects of Ukrain, a novel antitumor drug, on the activities of calcium, magnesium-dependent endonuclease (CME) and manganese-dependent endonuclease (MnDE) in rat liver nuclei, the activity of topoisomerase I assessed by pUC19 plasmid relaxation and CME activity in the nuclei of lymphocytes from colon cancer patients. Ukrain was found to exert a dose-dependent inhibiting effect on both CME and MnDE, similar to that exerted by erythropoietin, which was used as a reference preparation. Both Ukrain and erythropoietin also caused dose-dependent inhibition of topoisomerase I activity. The influence of Ukrain on CME activity in the nuclei of the lymphocytes of colon cancer patients was differential, depending on treatment efficacy. The results suggest that DNA-nicking enzymes may be a target of Ukrain and may mediate its antitumor effects.

Induction of apoptosis in cultured Chinese hamster ovary cells by Ukrain and its synergistic action with etoposide.

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.

Action of Ukrain, a cytostatic and immunomodulating drug, on effects of irradiation.

The ability of Ukrain, a cytostatic and immunomodulating semisynthetic compound of thiophosphate-modified alkaloids of Chelidonium majus L., to modify the effects of irradiation was studied in CBA/J mice using the dosage of the drug from 0.2 to 10 mg/kg. Ukrain was found to increase the survival rate of mice by 50-60 percent at irradiation doses from 6.00 to 6.75 Gy with no effect at the dose of 7.5 Gy. Varying the dosage of the drug did not influence the outcome of irradiation under experimental conditions employed. Maximal increase in the survival rate of the mice was noted when the drug was administered within the interval from 6 h before to 3 h after irradiation. It is noteworthy that under no circumstances did the administration of Ukrain result in a decrease in the survival rate of irradiated animals. The main outcome of the present study is the finding that Ukrain is capable of modifying the effects of irradiation when applied in both prophylactic and curative regimens. The effects of Ukrain are evident at doses from 0.2 to 10 mg/kg over the entire time-range studied and under doses of irradiation not exceeding LD 85/30. The drug was also found to be able to modify the effects of prolonged irradiation.

Potential therapeutic efficacy of Ukrain (NSC 631570) in AIDS patients with Kaposi's sarcoma.

In this study two case reports are presented of therapy with Ukrain, a semi-synthetic thiophosphoric acid compound of alkaloids isolated from Chelidonium majus L, for the treatment of AIDS patients with Kaposi's sarcoma. Ukrain was injected i.v. in the dose of 5 mg every other day for a total of 10 injections. During treatment the Kaposi's sarcoma lesions diminished in size, showed decolouration and no lesion appeared in the 30-day interval after the beginning of treatment. Both patients tolerated Ukrain well and showed an improved immunohaematological status: an increase in total leukocytes, T-lymphocytes and T-suppressor numbers. In one case T-helper lymphocytes were also increased. Future investigations are necessary for the evaluation of Ukrain efficacy in the treatment of this type of patients.