Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzopyrans / chemistry
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Butyrates / chemistry
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Dose-Response Relationship, Drug
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / drug effects
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Flavonoids / pharmacology*
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Hypopigmentation / chemically induced*
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Leupeptins / pharmacology
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Lysosomes / drug effects
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Lysosomes / metabolism
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Melanins / biosynthesis*
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Melanocytes / drug effects*
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Melanocytes / metabolism
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Mice
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Microphthalmia-Associated Transcription Factor / drug effects*
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Molecular Structure
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Monophenol Monooxygenase / metabolism*
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Proteasome Inhibitors
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Pyranocoumarins / chemistry
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Pyranocoumarins / isolation & purification*
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Pyranocoumarins / pharmacology*
Substances
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Benzopyrans
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Butyrates
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Flavonoids
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Leupeptins
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Melanins
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Microphthalmia-Associated Transcription Factor
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Proteasome Inhibitors
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Pyranocoumarins
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dihydropyranocoumarin D2
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decursin
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Monophenol Monooxygenase
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Extracellular Signal-Regulated MAP Kinases
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one