3‑HYDROXYQUINAZOLINE DERIVATIVE, AN ANALOGUE OF ERASTIN, INDUCES FERROPTOSIS IN METASTATIC MELANOMA CELLS

Abstract

Introduction. The main cause of clinical progression of tumor under the conditions of treatment is the resistance. Reactivate apoptosis in resistant to chemotherapy cells is impossible, the tumor grows into an irreversible growth phase. Recently published data on the ability of ferroptosis inducers to induce the death of resistant cells opens up new possibilities for improving the effectiveness of antitumor therapy.The purpose of the study\xa0– assessment of the mechanism of ferroptosis induction of the synthesized analogue of erastin OVN‑002 on Mel Z melanoma cells and investigation of its antitumor activity on transplanatated B‑16 melanoma of mice.Materials and methods. In this study 2D cultivation of metastatic Mel Z melanoma cells, phase‑contrast and fluorescence microscopy, and a model of experimental growth of B‑16 melanoma in female hybrids of immu‑ nocompetent mice F1 (C57Bl/6 × DBA / 2) were used. The antitumor effect was evaluated by measurement of tumor growth inhibition (TGI,\xa0 %) and increase of life span of the treated animals as compared to the control ones.Results. The cytotoxic activity of OVN‑002 was equal to the activity of erastin on metastatic melanoma cells Mel Z: 744 ± 20 and 719 ± 20 a. u., respectively. OVN‑002 at a dose 50\xa0mg / kg reduced the growth of experimental melanoma B‑16 about 81 % (TGI 81–57 %, p <0.05). The effect was stable up to 7th day, while erastin showed only a direct antitumor effect (TGI 65 %, p <0.05).Conclusion. The data obtained suggest that OVN‑002 might be considered as a novel antitumor agent.