Hypopigmentary action of dihydropyranocoumarin D2, a decursin derivative, as a MITF-degrading agent.
In this study, the decursin derivative dihydropyranocoumarin D2 (1) was selected for its effects on melanogenesis using a spontaneously immortalized mouse melanocyte cell line (Mel-Ab). The results showed that 1 effectively inhibited melanin synthesis in a concentration-dependent manner, but that it did not inhibit tyrosinase in a cell-free system. In addition, the changes in ERK, Akt, and microphthalmia-associated transcription factor (MITF) in response to treatment with 1 were assessed. The results revealed that ERK was dramatically up-regulated and MITF was down-regulated in response to treatment with 1, but that Akt was unchanged. Therefore, the effects of 1 on melanogenesis were examined in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway). PD98059 restored hypopigmentation and the down-regulation of MITF induced by 1. Finally, MITF down-regulation by 1 was clearly restored by both chloroquine, a lysosomal proteolysis inhibitor, and MG132, a proteasome inhibitor.
Kim
Dong-Seok
DS
Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-Dong Dongjak-Gu, Seoul 156-756, Korea.
Park
So-Hee
SH
Lee
Hyun-Kyung
HK
Choo
Soo-Jin
SJ
Lee
Jee Hyun
JH
Song
Gyu Yong
GY
Yoo
Ick-Dong
ID
Kwon
Sun-Bang
SB
Na
Jung-Im
JI
Park
Kyoung-Chan
KC
D000818:Animals; D001578:Benzopyrans / Q000737:chemistry; D002087:Butyrates / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D017496:Hypopigmentation / Q000139:chemically induced*; D007976:Leupeptins / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000187:drug effects*; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D061988:Proteasome Inhibitors; D039681:Pyranocoumarins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D001578:Benzopyrans; D002087:Butyrates; D005419:Flavonoids; D007976:Leupeptins; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D061988:Proteasome Inhibitors; D039681:Pyranocoumarins; C549869:dihydropyranocoumarin D2; C101278:decursin; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one