New biochemical mechanisms of the anticancer effect of Ukrain in the treatment of cancer of the urinary bladder.

The aim of this study was to elucidate the mechanisms of the anticancer effect of Ukrain by comparing the processes of formation of the pool of free amino acids and their derivatives in the blood plasma and tumor biopsy specimens and unchanged bladder tissue in 28 patients with T1N0M0 bladder cancer. The examination was carried out before and after Ukrain treatment (10 mg i.v./day, for 20 days), which was combined with systemic chemotherapy for bladder cancer. Twenty-eight patients served as controls and received systemic chemotherapy only. Compared with healthy donors, the blood plasma of patients with urinary bladder cancer showed decreased concentrations of thiol-containing free amino acids and glutamine (Gln) and increased levels of nonessential (glutamic acid, proline, alanine) and aromatic (phenylalanine) free amino acids. In contrast to conventional chemotherapy, treatment with Ukrain eliminated the blood plasma amino acid imbalance in patients with bladder cancer, concomitantly enriching the pool of free amino acids and their derivatives in unchanged urinary bladder tissue and decreasing concentrations of Gln and leucine (Leu), regulators of malignant cell proliferation and differentiation, by 30-50%. In this situation, the concentrations of Gln and Leu in tumor tissue and the surrounding healthy urinary bladder tissue correlated highly significantly and negatively (r = -0.95). In conclusion, Ukrain prevents active free amino acid transport into urinary bladder tumor tissue, inhibiting the activities of protein biosynthesis, gluconeogenesis and energy production. The combined decrease in Gln and Leu levels in urinary bladder tumor tissue is a specific sign of the antitumor effect of Ukrain and a mechanism of its cancerostatic action by controlling the processes of amino acid pool formation in the tumor.