Eicosa-11Z,14Z,17Z-Trienoic Acid Suppresses Melanogenesis by Inhibiting Intracellular MITF/Tyrosinase Axis.

Eicosa-11Z,14Z,17Z-trienoic acid (ETA; 20:3 n-3) is an ω-3 polyunsaturated fatty acid whose role in melanogenesis remains unclear. This study investigated the effects of ETA on melanogenesis using α-MSH-stimulated B16F10 melanoma cells and explored the underlying mechanisms. Structural similarity analysis indicated that ETA is closely related to α-linolenic acid, a lipid known to influence pigmentation. ETA showed minimal direct inhibition of mushroom tyrosinase activity in a cell-free system. In cell-based assays, ETA did not induce significant cytotoxicity within the tested concentration range. Under melanogenic conditions, ETA reduced α-MSH-induced melanin accumulation and intracellular tyrosinase activity. This reduction was accompanied by decreased mRNA expression of Tyr, Tyrp1, and Tyrp2, together with reduced protein expression of MITF, tyrosinase, TYRP1, and TYRP2. ETA also attenuated α-MSH-induced phosphorylation of CREB, ERK, and MITF. Immunofluorescence analysis further showed that ETA reduced α-MSH-induced MITF fluorescence intensity, including signals observed in the nuclear region. Taken together, these findings suggest that ETA modulates melanogenesis-related processes in B16F10 cells, likely through mechanisms involving changes in MITF localization and downstream gene expression rather than direct inhibition of tyrosinase activity. These results suggest that ETA may represent a potential candidate for further investigation in the context of pigmentation regulation.