Effect of Rosmarinic Acid and Ionizing Radiation on Glutathione in Melanoma B16F10 Cells: A Translational Opportunity.

To explain a paradoxical radiosensitizing effect of rosmarinic acid (RA) on the melanoma B16F10 cells, we analyzed the glutathione (GSH) intracellular production on this cell (traditionally considered radioresistant) in comparison with human prostate epithelial cells (PNT2) (considered to be radiosensitive). In PNT2 cells, the administration of RA increased the total GSH content during the first 3 h (p < 0.01) as well as increased the GSH/ oxidized glutathione (GSSG) ratio in all irradiated cultures during all periods studied (1h and 3h) (p < 0.001), portraying an increase in the radioprotective capacity. However, in B16F10 cells, administration of RA had no effect on the total intracellular GSH levels, decreasing the GSH/GSSG ratio (p < 0.01); in addition, it caused a significant reduction in the GSH/GSSG ratio in irradiated cells (p < 0.001), an expression of radioinduced cell damage. In B16F10 cells, the administration of RA possibly activates the metabolic pathway of eumelanin synthesis that would consume intracellular GSH, thereby reducing its possible use as a protector against oxidative stress. The administration of this type of substance during radiotherapy could potentially protect healthy cells for which RA is a powerful radioprotector, and at the same time, cause significant damage to melanoma cells for which it could act as a radiosensitive agent.