CD437 increases the iron uptake by metastatic melanoma cells

Abstract

Background. CD437, an analog of vitamin A, is an agonist of the retinoic acid γ-receptor (RARγ). CD437 is also known to cause p53-independent DNA damage by a mechanism independent of the RAR-mediated pathway. In cancer patients, iron deficiency is constantly detect, the delivery of iron to tissues is also destroyed.Aim. To study the effect of CD437 on iron metabolism in metastatic melanoma cells, Mel Z.Materials and methods. In this study 2D cultivation of metastatic Mel Z melanoma cells, phase-contrast and fluorescence microscopy, flow cytofluorimetry were used.Results. In control cells without the addition of CD437 CD71, transferrin receptor, expressed 40 ± 4 % (p <0.05) of Mel Z cells, in the presence of CD437 CD71 expression increased to 80 ± 6 %. Next, we have studied the expression of ferritin. Iron, which is not involved in cell metabolism, is bound by ferritin. In control experiments, ferritin was expressed by 84 ± 6 % (p <0.05) of cells. When the cells grew in the presence of CD437, ferritin was expressed by all the cells (100 %, p <0.05). Such a scenario indicates that CD437 may contribute to the accumulation of free, unbound iron in the cell, which can induce ferroptosis. In control experiments without the addition of CD437, the level of membranes lipid peroxidation, an indicator of ferroptosis, was insignificant. Lipid peroxidation induced by CD437 was 55 ± 5 % (p <0.05) of the fluorescence intensity induced by erastin, positive control.Conclusion. CD437 increases the iron uptake by metastatic melanoma cells. The low level of membranes lipid peroxidation induced by CD437 does not allow it to be considered as an inducer of ferroptosis. Additional investigations are needed to find iron-binding targets alternative to ferritin.