Hypopigmentary action of dihydropyranocoumarin D2, a decursin derivative, as a MITF-degrading agent

J Nat Prod. 2010 May 28;73(5):797-800. doi: 10.1021/np900455j.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzopyrans / chemistry
  • Butyrates / chemistry
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / drug effects
  • Flavonoids / pharmacology*
  • Hypopigmentation / chemically induced*
  • Leupeptins / pharmacology
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Melanins / biosynthesis*
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / drug effects*
  • Molecular Structure
  • Monophenol Monooxygenase / metabolism*
  • Proteasome Inhibitors
  • Pyranocoumarins / chemistry
  • Pyranocoumarins / isolation & purification*
  • Pyranocoumarins / pharmacology*

Substances

  • Benzopyrans
  • Butyrates
  • Flavonoids
  • Leupeptins
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Proteasome Inhibitors
  • Pyranocoumarins
  • dihydropyranocoumarin D2
  • decursin
  • Monophenol Monooxygenase
  • Extracellular Signal-Regulated MAP Kinases
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one