Jeong Yoon Ju, Lee Jae-Young, Park Jino, Park Soo Nam
Department of Fine Chemistry, Cosmetic R&D Center, Cosmetic Industry-Coupled Collaboration Center, Seoul National University of Science and Technology, 232 Gongneung-ro, Nowon-gu, Seoul 01811, Republic of Korea.
Daebong LS Ltd., 692-8, Gojan-dong, Namdong-gu, Incheon 21697, Republic of Korea.
Life Sci. 2017 Dec 15;191:52-58. doi: 10.1016/j.lfs.2017.10.009. Epub 2017 Oct 7.
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.
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.
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.
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.
报告一种新型丁香酸衍生物（R）-乙基-2-乙酰氨基-3-（4-羟基-3,5-二甲氧基苯甲酰硫基）丙酸酯（EABTO）对黑色素合成的影响，并确定其在B16F1黑色素瘤细胞中的作用机制。
评估EABTO对B16F1细胞和人表皮黑素细胞中黑色素合成的影响以及对无细胞酪氨酸酶活性的影响。通过蛋白质免疫印迹法研究EABTO诱导的细胞信号级联反应。
EABTO以剂量依赖性方式有效降低黑色素合成，但对无细胞酪氨酸酶活性无影响。EABTO显著降低酪氨酸酶、酪氨酸酶相关蛋白1（TRP-1）和TRP-2等黑素生成酶的表达。EABTO降低磷酸化的cAMP反应元件结合蛋白（CREB）和环磷酸腺苷（cAMP）的量，从而抑制小眼相关转录因子（MITF）的表达。此外，EABTO上调磷酸化的ERK。一种特异性ERK途径抑制剂PD98059可降低EABTO诱导的ERK磷酸化，并恢复MITF的表达和黑色素含量。
EABTO通过抑制cAMP-CREB途径和激活ERK来抑制B16F1黑色素瘤细胞中的黑色素生成，从而降低MITF和黑素生成酶的表达。
