{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:23:28Z","timestamp":1790223808186,"version":"4.1.0"},"reference-count":95,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014434","name":"Polish National Agency for Academic Exchange","doi-asserted-by":"publisher","award":["BPI\/PST\/2024\/1\/00008"],"award-info":[{"award-number":["BPI\/PST\/2024\/1\/00008"]}],"id":[{"id":"10.13039\/501100014434","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BPI\/PST\/2024\/1\/00008"],"award-info":[{"award-number":["BPI\/PST\/2024\/1\/00008"]}],"id":[{"id":"https:\/\/ror.org\/02jf81j23","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Ultraviolet A (UVA) radiation disrupts the redox balance of melanocytes and may lead to the development of melanoma, highlighting the need for new skin protection strategies. This study assessed the effect of phytocannabinoids [cannabigerol (CBG), cannabidiol (CBD), and CBG + CBD] on redox homeostasis in control and UVA-exposed melanocytes and in melanoma cells (SK-Mel-5). UVA radiation increased the activity of prooxidant enzymes in both melanocytes and SK-Mel-5 cells and, consequently, the level of reactive oxygen species (ROS) (approx. 2-fold). It also activated nuclear factor erythroid 2 (Nrf2), as reflected by increased expression of heme oxygenase 1 (HO-1) (melanocytes approx. 2-fold; SK-Mel-5 approx. 7-fold). Concomitantly, antioxidant mechanisms were impaired, as demonstrated by reduced superoxide dismutase (SOD1\/SOD2) activity and impaired glutathione and thioredoxin function. These changes were accompanied by increased levels of oxidative damage markers (isoprostanes, 4-hydroxynonenal-4-HNE, and 4-HNE-protein adducts) (43\u2013100%) and increased inflammatory signaling, including increased expression of nuclear factor kappa B (NF-\u03baB) subunits (melanocytes: p52 ~2-fold, p65 ~75%; SK-Mel-5: ~4\u20134.5-fold) and tumor necrosis factor alpha (TNF-\u03b1; ~30%). Phytocannabinoid treatment modulated these UVA-induced changes. In SK-Mel-5 cells, phytocannabinoids normalized the activity of prooxidant enzymes and consequently reduced ROS levels (~30%). They also reduced Nrf2 activation and HO-1 expression; however, CBG increased HO-1 level in melanocytes (~25\u201340%). Furthermore, phytocannabinoids enhanced antioxidant defense by increasing SOD activity, particularly in melanocytes (~10\u201340%), and restoring the glutathione and thioredoxin systems. Markers of oxidative damage were reduced by approximately 23\u201337% after treatment. Furthermore, phytocannabinoids attenuated NF-\u03baB activation (p52 ~18\u201328%, p65 ~25\u201329% in melanocytes; ~20% in SK-Mel-5), while TNF-\u03b1 levels remained unchanged. The effects in non-irradiated cells were modest (&lt;15%). These results suggest that phytocannabinoid-mediated modulation of redox balance may stabilize melanocytes exposed to UVA radiation and potentially reduce the risk of neoplastic transformation. However, the observed protective effects in SK-Mel-5 cells require further investigation and detailed molecular analysis.<\/jats:p>","DOI":"10.3390\/antiox15060690","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:33:14Z","timestamp":1780479194000},"page":"690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Metabolic Responses of Melanocytes and Melanoma Cells to UVA Radiation and Phytocannabinoids Exposure"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9101-5125","authenticated-orcid":false,"given":"Micha\u0142","family":"Biernacki","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Gieniusz","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5240-1346","authenticated-orcid":false,"given":"Agnieszka","family":"G\u0119gotek","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5051-1843","authenticated-orcid":false,"given":"Morana","family":"Jaganjac","sequence":"additional","affiliation":[{"name":"Laboratory for Oxidative Stress, Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5397-7139","authenticated-orcid":false,"given":"El\u017cbieta","family":"Skrzydlewska","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Medical University of Bialystok, Mickiewicza 2D, 15-222 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","first-page":"dev201266","article-title":"Melanocyte Lineage Dynamics in Development, Growth and Disease","volume":"151","author":"Brombin","year":"2024","journal-title":"Dev. 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