np400129z_si_001.pdf (508.23 kB)
Caffeic Acid Phenethyl Ester Inhibits Alpha-Melanocyte Stimulating Hormone-Induced Melanin Synthesis through Suppressing Transactivation Activity of Microphthalmia-Associated Transcription Factor
journal contribution
posted on 2013-08-23, 00:00 authored by Ji-Yeon Lee, Hee-Jung Choi, Tae-Wook Chung, Cheorl-Ho Kim, Han-Sol Jeong, Ki-Tae HaCaffeic acid phenethyl ester (1), a natural compound found in various plants and propolis,
is a well-known anti-inflammatory, immunomodulatory, and cytotoxic
agent. The present study aimed to investigate the molecular events
underlying the antimelanogenic activity of 1 in alpha-melanocyte
stimulating hormone (α-MSH)-stimulated B16-F10 melanoma cells.
In this investigation, 1 effectively reduced α-MSH-stimulated
melanin synthesis by suppressing expression of melanogenic enzymes
such as tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related
protein-2 (TRP-2), although this compound did not directly inhibit
tyrosinase enzyme activity. On the other hand, the expression and
nuclear translocation of microphthalmia-associated transcription factor
(MITF) as a key transcription factor for tyrosinase expression regulating
melanogenesis were not affected by treatment with 1.
The upstream signaling pathways including cAMP response element-binding
protein (CREB), glycogen synthase kinase-3β (GSK-3β),
and Akt for activation and expression of MITF were also not influenced
by 1. Interestingly, 1 inhibited transcriptional
activity of a tyrosinase promoter by suppressing the interaction of
MITF protein with an M-box containing a CATGTG motif on the tyrosinase
promoter. Given the important role of MITF in melanogenesis, suppression
of 1 on the function of MITF to transactivate tyrosinase
promoter may present a novel therapeutic approach to treat hyperpigmentation
disorders.