10(E)-Pentadecenoic Acid Inhibits Melanogenesis Partly Through Suppressing the Intracellular MITF/Tyrosinase Axis

• Published in: Antioxidants 2024-12, Vol.13 (12), p.1547
• Main Authors: Lee, Min-Kyeong, Moon, Kyoung Mi, Park, Su-Yeon, Seo, Jaeseong, Kim, Ah-Reum, Lee, Bonggi
• Format: Article
• Language: English
• Subjects: 10(E)-pentadecenoic acid; Cytotoxicity; Enzymes; Fatty acids; Fibroblasts; Free radicals (Chemistry); Intermedin; Intracellular; Kinases; Lipids; Melanin; Melanocyte-stimulating hormone; melanogenesis; Melanoma; Metabolism; Microphthalmia-associated transcription factor; MITF; Nuclear transport; Pigmentation; Proteins; RNA; Skin; Skin diseases; Skin pigmentation; tyrosinase
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox13121547

Melanogenesis, the biological process responsible for melanin synthesis, plays a crucial role in determining skin and hair color, photoprotection, and serving as a biomarker in various diseases. While various factors regulate melanogenesis, the role of fatty acids in this process remains underexplored. This study investigated the anti-melanogenic properties of 10(E)-pentadecenoic acid (10E-PDA) through both in silico and in vitro analyses. SwissSimilarity was utilized to predict the functional properties of 10E-PDA by comparing it with structurally similar lipids known to exhibit anti-melanogenic effects. Subsequent in vitro experiments demonstrated that 10E-PDA significantly reduced melanin production and intracellular tyrosinase activity in α-MSH (melanocyte-stimulating hormone)-stimulated B16F10 melanoma cells without exhibiting significant cytotoxicity at concentrations up to 15 μM. Further mechanistic studies revealed that 10E-PDA inhibited the nuclear translocation of microphthalmia-associated transcription factor (MITF), consistent with the decrease observed in p-MITF protein levels. It also decreased the mRNA levels of tyrosinase-related proteins (TRP-1, TRP-2) and tyrosinase, while reducing the protein levels of TRP-1 and tyrosinase, but not TRP-2. These findings suggest that 10E-PDA exerts its anti-melanogenic effects by modulating the MITF/tyrosinase axis, presenting potential therapeutic implications for skin pigmentation disorders.