CYTOTOXIC ACTIVITY OF THE IONOPHORE ANTIBIOTIC SALINOMYCINAND ITS COMBINATION WITH ANTICANCER PREPARATIONS AGAINST HUMAN MELANOMA CELLS

E.Yu. Moskaleva, I.G. Kondrasheva, O.N. Popova, Yu.P. Semochkina, A.M. Shmargun, S.E. Severin
National Research Centre «Kurchatov Institute», Moscow, Russian Federation

Salinomycin is referred to the group of the polyether antibiotics with ionophore activity. Currently salinomycin is considered as a potential anticancer drug. The aim of this work was to investigate the cytotoxic activity of salinomycin against MDR1+ (Mel-8) and MDR1- (Mel-10) of human melanoma cells and cells that form the side population (SP), and the ability of salinomycin to sensitize melanoma cells to the action of such anticancer drugs as doxorubicin and dacarbazine. MDR1+ and MDR1- melanoma cells were shown to be sensitive to salinomycin. Salinomycin acts in melanoma cells as an inhibitor of protein РgP and possibly as an inhibitor of some other ABC-transporters.It inhibits the accumulation of mitoxantrone, doxorubicin, and rhodamine-123 not only in MDR1+, but in the MDR1- melanoma cells reduces the size of the fraction of melanoma cells that form the SP. In addition, the drug sensitizes human melanoma cells to the action of doxorubicin and dacarbazine when it was added to the cells for 24 hours prior to the addition of these drugs.
Keywords: 
salinomycin, melanoma, MDR1, rhodamine-123, SP, cancer stem cells, sensitization, doxorubicin, dacarbazine

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