Cytotoxic effects of cannabidiol on human metastatic melanoma cells: a potential therapeutic strategy?

Background: Melanoma is the most aggressive form of skin cancer, responsible for the majority of skin cancer-related deaths due to its high metastatic potential and resistance to treatment [1]. The limited efficacy of systemic therapies in treating this disease underscores the need to explore novel therapeutic strategies. Cannabidiol (CBD), a bioactive compound from Cannabis sativa, has shown anticancer properties in various cancer models [2,3]. However, its effects on melanoma cells and its potential selectivity remain under investigation. Objective: This study evaluates the cytotoxic effects of CBD on human metastatic melanoma cells. Methods: Two melanoma cell lines (A375 and MeWo) and a normal human keratinocyte cell line (HaCaT) were treated with CBD (0.05-100 µM) for 24 and 48 hours. Cell viability was assessed by the MTT assay, and morphological changes were analyzed by inverted light microscopy. Results: CBD reduced cell viability in a concentration-dependent manner in all cell lines. HaCaT cells were the most sensitive with IC50 values at 24 h of 4.1 µM, followed by A375 (IC50 5.1 µM) and MeWo (IC50 5.8 µM) cells. Similar values were observed at 48 h (p > 0.05), indicating no significant time-dependent effect. Morphological changes were observed in all cell lines, becoming more pronounced with increasing CBD concentration and exposure time. Conclusions: CBD is a promising candidate for melanoma management. However, its non-selective cytotoxicity toward melanoma cells remains a major challenge for safe clinical application. Ongoing research aims to elucidate the molecular mechanisms underlying CBD-induced cytotoxicity and to explore strategies for improving selectivity, potentially enhancing its clinical applicability in melanoma treatment.