Dietary Polyphenols Curcumin and Resveratrol Exert Selective Anticancer Effects in Melanoma Cells

Background/Objectives: Although curcumin (CUR) and resveratrol (RSV) are natural polyphenolic compounds with reported anticancer and anti-inflammatory properties, their combined anticancer effects in melanoma cells remain incompletely characterized. This study aimed to evaluate the anticancer efficacy of CUR and RSV, individually, and in combination, in melanoma cells compared to normal melanocytes. Methods: Cell viability and intracellular ATP levels were quantified, and dose–response analyses performed. Cellular morphology and nuclear alterations were examined by phase-contrast microscopy and DAPI staining. Cell cycle distribution and apoptosis were analyzed by Muse™ Cell Analyzer with dedicated assay kits. Survival- and death-related signaling proteins were evaluated by Western blotting. Results: Combined treatment with CUR (60 μM) and RSV (40 μM) for 48 h synergistically reduced melanoma cell viability and markedly depleted intracellular ATP levels, while exerting minimal cytotoxic effects on normal melanocytes. CUR/RSV co-treatment induced pronounced morphological and nuclear alterations, significantly increased apoptotic cell populations, and modulated key signaling pathways regulating cell survival and programmed cell death in melanoma cells. Conclusions: These findings demonstrate that combined CUR and RSV treatment exerts enhanced, melanoma-selective anticancer activity while sparing normal melanocytes. The results provide a strong experimental rationale for further in vivo validation of CUR/RSV-based combination strategies as a potential therapeutic approach for melanoma.