Radiomodulatory effects of rosmarinic acid in melanocytic cells

Purpose: To characterize the radiomodulatory effects of rosmarinic acid (RA) in non‑tumoural epithelial cells and melanocytic cell lines and to assess whether RA can protect normal cells while losing radioprotective capacity in melanin‑producing cells.Materials and Methods Four cell lines with differing degrees of radiosensitivity were employed: PNT2 (non-tumoral prostate epithelial cells used as reference), MELAN A (normal murine melanocytes), SK-MEL-1 (human metastatic melanoma cells), and B16F10 (murine metastatic melanoma cells). Cell survival assays, apoptosis, intracellular glutathione status, and cell cycle progression were evaluated 48 hours following exposure to 20 Gy X-rays, with or without RA pretreatment at 25 µM administered 15 minutes before irradiation.Results In PNT2 cells, RA conferred robust radioprotection with a protection factor of 99 ± 1.0% (p < .001), reducing radiation-induced apoptosis by more than 300%, significantly increasing the GSH/GSSG ratio, and normalizing cell cycle distribution. In MELAN-A and SK-MEL-1 cells, RA abolished radioprotection, reduced the GSH/GSSG ratio, and increased the apoptotic fraction. In B16F10 cells, RA tripled radiation-induced cell death (p < .001), further depleted the GSH/GSSG ratio, increased apoptosis, and markedly aggravated G2/M arrest, demonstrating a frank and significant radiosensitizing effect. The loss of radioprotective capacity is: B16F10 > Melan-A = SK-MEL-1 > PNT2 (p < .001).Conclusions RA exhibits a cell-type-dependent radiomodulatory profile: it effectively protects normal epithelial cells while losing its radioprotective capacity—or acting as a radiosensitizer—in melanin-producing cells. Confirmation of this selectivity in vivo studies could represent a promising strategy to widen the therapeutic window in melanoma radiotherapy.