Exp Mol Med.  2013 Apr;45(4):e17.

Glyceollins, a novel class of soybean phytoalexins, inhibit SCF-induced melanogenesis through attenuation of SCF/c-kit downstream signaling pathways

• Shin SH
• Lee YM

Abstract

The anti-melanogenesis effect of glyceollins was examined by melanin synthesis, tyrosinase activity assay in zebrafish embryos and in B16F10 melanoma cells. When developing zebrafish embryos were treated with glyceollins, pigmentation of the embryos, melanin synthesis and tyrosinase activity were all decreased compared with control zebrafish embryos. In situ expression of a pigment cell-specific gene, Sox10, was dramatically decreased by glyceollin treatment in the neural tubes of the trunk region of the embryos. Stem cell factor (SCF)/c-kit signaling pathways as well as expression of microphthalmia-associated transcription factor (MITF) were determined by western blot analysis. Glyceollins inhibited melanin synthesis, as well as the expression and activity of tyrosinase induced by SCF, in a dose-dependent manner in B16F10 melanoma cells. Pretreatment of B16F10 cells with glyceollins dose-dependently inhibited SCF-induced c-kit and Akt phosphorylation. Glyceollins significantly impaired the expression and activity of MITF. An additional inhibitory function of glyceollins was to effectively downregulate intracellular cyclic AMP levels stimulated by SCF in B16F10 cells. Glyceollins have a depigmentation/whitening activity in vitro and in vivo, and that this effect may be due to the inhibition of SCF-induced c-kit and tyrosinase activity through the blockade of downstream signaling pathway.

Keyword

c-kit; cyclic AMP; glyceollins; melanogenesis; signaling pathways; stem cell factor

MeSH Terms

Animals
Embryo, Nonmammalian/drug effects
Melanins/*biosynthesis
Melanoma, Experimental/metabolism/pathology
Mice
Monophenol Monooxygenase/metabolism
Phosphorylation/drug effects
Pigmentation/drug effects
Proto-Oncogene Proteins c-kit/*metabolism
Pterocarpans/chemistry/*pharmacology
SOXE Transcription Factors/metabolism
Sesquiterpenes/chemistry/*pharmacology
Signal Transduction/*drug effects
Soybeans/*chemistry
Stem Cell Factor/*pharmacology
Zebrafish/embryology/metabolism
Melanins
Pterocarpans
SOXE Transcription Factors
Sesquiterpenes
Stem Cell Factor
Monophenol Monooxygenase
Proto-Oncogene Proteins c-kit