Aims: To report the effects of a novel syringic-acid derivative, (R)-ethyl-2-acetamido-3-(4-hydroxy-3,5-dimethoxybenzoylthio)propanoate (EABTO), on melanin synthesis and to identify its mechanism of action in B16F1 melanoma cells.
Methods: The effects of EABTO on melanin synthesis in B16F1 cells and human epidermal melanocytes and the influence on cell-free tyrosinase activity were evaluated. EABTO-induced cellular signaling cascades were studied by western blotting.
Key findings: EABTO effectively decreased melanin synthesis in a dose-dependent manner but had no effect on cell-free tyrosinase activity. EABTO significantly decreased the expression of melanogenic enzymes such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2. EABTO decreased the amounts of phosphorylated cAMP response element-binding protein (CREB) and cyclic adenosine monophosphate (cAMP), thereby inhibiting expression of microphthalmia-associated transcription factor (MITF). Moreover, EABTO upregulated phosphorylated ERK. A specific ERK pathway inhibitor, PD98059, reduced EABTO-induced ERK phosphorylation and restored the expression of MITF and melanin content.
Significance: EABTO inhibits melanogenesis in B16F1 melanoma cells via suppression of the cAMP-CREB pathway and activation of ERK, thus decreasing expression of MITF and of melanogenic enzymes.
Keywords: ERK; MITF; Melanogenesis; Syringic-acid derivative; Tyrosinase.
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