A comparative assessment of the effects of alkaloid tryptanthrin, rosmarinic acid, and doxorubicin on the redox status of tumor and immune cells

Abstract

A comparative study of the effects of natural compounds with different biological activity spectra and mechanisms of action on the dynamics of the change in the redox-status of tumor and immune cells was carried out by measuring the intracellular level of reactive oxygen species depending on the dose and incubation time. The quinazoline alkaloid tryptanthrin, phenol propanoid rosmarinic acid, and the anticancer agent doxorubicin were tested. This study was performed on Ehrlich adenocarcinoma tumor cells and splenocytes after loading with the oxidant sensing fluorescent probe 2′,7′-dichlorofluorescein diacetate. It was shown that when rosmarinic acid influences tumor cells it has a pronounced antioxidant activity at a low dose (1 mg/mL), while a high dose of rosmarinic acid (10 mg/mL) exhibits prooxidant activity. Interestingly, in a splenocyte cell culture, rosmarinic acid reduced the level of reactive oxygen species at low and high doses. The combined application of doxorubicin with rosmarinic acid at a low dose reduced the prooxidant effect of doxorubicin, which is a potent inducer of reactive oxygen species in tumor cells. Tryptanthrin is also a potent inducer of reactive oxygen species with respect to tumor and immune cells; it is a more potent prooxidant than doxorubicin. In addition, tryptanthrin enhanced the doxorubicin-induced formation of reactive oxygen species by tumor cells in the combined use of doxorubicin with tryptanthrin. However, the prooxidant effect of tryptanthrin is short-term and decreases after a prolonged incubation. The effect of reactive oxygen species on the potent mechanisms of the biological activities of the individual and combined substances under study is discussed.