Effect of polyfunctional selenium-containing phenolic antioxidants on the activity of antitumor cytostatics and their combinations with a nitric oxide donor in vivo

The influence of a newly synthesized chemical substance from the class of synthetic alkylated phenols with the hydrophilic chalcogen-containing derivative, potassium 3-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propylseleno]propionate (PEC), on the antitumor activity in animals with leukemia P388 was studied. The administration of PEC to the animals with leukemia P388 increases the life span of the animals by 3.5 times (from 9.2 to 32 days) compared to the uncured control depending on the concentration of the introduced substance. The interaction of a combination of selenium-containing phenolic antioxidant PEC with the nitric oxide donor (NaNO₂) and three antitumor cytostatics, cyclophosphamide (CP), cisplatin (cPt), and doxorubicin (Dox), was studied in vivo on a model of lymphocytic leukemia P388 of BDF₁ mice. The selenium-containing phenolic antioxidant exhibited a higher activity than previously studied sodium 3-(3′-tert-butyl-4′-hydroxyphenyl)propylthiosulfate (TS-13). Like the sulfur-containing antioxidant TS-13, PEC induces oppositely directed changes in the activity of the studied cytostatics depending on the concentration: the change is potentiating for chemotherapy with CP and cPt and inhibiting for chemotherapy with Dox. It is most likely that the addition of the nitric oxide donor (NaNO₂) to the studied compositions changes the redox potential of the cells, which affects the modulation of the activity of the cytostatics under study. The regime of metronomic chemotherapy of tumors is most efficient: the maximum tolerance dose is introduced first, and then (from the third to seventh day) the subtherapeutic dose is administrated.