Background: Ultraviolet A (UVA) radiation is a major environmental factor contributing to melanoma development. Melanocytes synthesize melanin, which provides partial protection against UVA-induced oxidative damage; however, these cells remain highly susceptible to oxidative and pro-inflammatory effects of UVA exposure. Methods: In melanocytes, the following parameters were assessed: total antioxidant status (TAS-photometrically), reactive oxygen species (ROS-ESR), lipid peroxidation (4-HNE-GC-MS/MS), 4-HNE-protein adducts, and the expression/localization of key signaling proteins including phosphorylated nuclear factor erythroid 2-related factor 2 (pNrf2) and nuclear factor kappa B (NFκB) subunits ELISA/fluorescence microscopy. Results: Cannabigerol (CBG) is a cytoprotective phytocannabinoid. In vitro studies showed that CBG attenuated UVA-induced oxidative stress in human melanocytes exposed to UVA radiation and significantly reduces lipid peroxidation, as measured by the levels of 4-hydroxynonenal (4-HNE) and its protein adducts. The biosynthesis of antioxidants was also regulated by CBG, even when administered post-irradiation. CBG attenuated the effects of UVA radiation by downregulating Nrf2, Kelch-like ECH-associated protein 1 (Keap1), BTB domain and CNC homolog 1 (Bach1), potent cyclin-dependent kinase inhibitor (p21), KRAB-associated protein 1 (KAP1), and multifunctional adaptor protein (p62). CBG also partially inhibited the pro-inflammatory NFκB signaling pathway by reducing the level of the activator (pIκB) and increasing the levels of the inhibitors (IKKα/β). Conclusion: These results suggest that CBG may protect melanocytes from UVA-induced oxidative changes and lipid peroxidation by activating the Nrf2-dependent antioxidant system and inhibiting NFκB-based pro-inflammatory signaling. CBG can therefore create favorable conditions for the physiological functioning of melanocytes after UVA exposure, ultimately reducing the risk of inflammatory skin responses and neoplastic transformation.
Jarocka-Karpowicz et al. (Fri,) studied this question.