Nicotinamide Counteracts Ultraviolet-B-Induced Cytotoxic Effects and Aquaporins Overexpression in the A375 Melanoma Cell Line

Background/objectives: Ultraviolet-B (UVB) represents a major extrinsic factor in skin cancer development, causing cellular changes that are not yet fully understood. Aquaporins (AQPs) are a family of transmembrane proteins that favor water transport and are involved in several pathways. Nicotinamide (NAM), a vitamin B3 derivate, is a safe molecule able to reduce UVB-induced damages. This study aims to verify whether AQP expression is affected by UVB exposure at different dosages and times and to evaluate NAM’s effects against UVB-induced damages. Methods: A375 cells were exposed to 40, 100, and 200 mJ/cm² UVB doses and analyzed 0, 1, 18, and 24 h post-irradiation. Results: We found that the 40 mJ/cm² UVB dose, 24 h post-irradiation, caused the most detrimental effects an overall overexpression and dimerization of AQPs. However, in the presence of NAM 25 μM, the cell cycle was restored, leading to improved cell viability and proliferation, reduced ROS levels, and reduced DNA damage. Moreover, we found decreased AQPs expression and dimerization. Conclusions: Overall, NAM effectively mitigates UVB-induced cellular damage, including AQPs overexpression, and may serve as a protective agent against UVB-related skin damage.