N-(4-bromophenethyl) Caffeamide Inhibits Melanogenesis by Regulating AKT/Glycogen Synthase Kinase 3 Beta/Microphthalmia-associated Transcription Factor and Tyrosinase-related Protein 1/Tyrosinase

Author(s): Yueh-Hsiung Kuo, Chien-Chia Chen, Ping Lin, Ya-Jhen You, Hsiu-Mei Chiang

Journal Name: Current Pharmaceutical Biotechnology

Volume 16 , Issue 12 , 2015

Become EABM
Become Reviewer
Call for Editor


Skin color is primarily produced by melanin, which is a crucial pigment that protects the skin from UV-induced damage and prevents carcinogenesis. However, accumulated melanin in the skin may cause hyperpigmentation and related disorders. Melanin synthesis comprises consecutive oxidative reactions, and tyrosinase is the enzyme that catalyzes the rate-limiting process of melanogenesis. In this study, tyrosinase-related protein 1 (TRP-1) and TRP-2 contributed to melanin formation. N-(4-bromophenethyl) caffeamide ((E)-N-(4-bromophenethyl)-3-(3,4-dihydroxyphenyl)acrylamide; K36H), a caffeic acid phenyl amide derivative, inhibited α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and tyrosinase activity in B16F0 cells. In addition, K36H reduced the protein expression of the phospho-cAMP response element binding protein (p-CREB), microphthalmia-associated transcription factor (MITF), tyrosinase, and TRP-1. Moreover, K36H promoted AKT and glycogen synthase kinase 3 beta (GSK3β) phosphorylation, thereby inhibiting MITF transcription activity. Thus, K36H attenuated α-MSH-induced cAMP pathways, contributing to hypopigmentation. The results of a safety assay revealed that K36H did not exhibit cytotoxicity or irritate the skin or eyes. According to these results, K36H may have the potential to be used as a whitening agent in the cosmetic and pharmaceutical industries.

Keywords: Melanogenesis, N-(4-bromophenethyl) caffeamide, microphthalmia-associated transcription factor (MITF), cAMP response element binding protein (CREB), tyrosinase-related protein (TRP).

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2015
Page: [1111 - 1119]
Pages: 9
DOI: 10.2174/1389201016666150817094258
Price: $65

Article Metrics

PDF: 23