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

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. Skin pigmentation: How soy compounds affect melanin production A group of plant compounds, produced by soybeans in response to pathogens, prevent the production of melanin pigments in fish and mammalian models. This discovery, by Sun-Hye Shin and You-Mie Lee of Kyungpook National University in Korea, could lead to new cosmetic agents for people with hyper-pigmentation following inflammatory skin disease. Lee and colleagues previously showed that the soy compounds, called glyceollins, inhibit melanin synthesis in mouse melanoma cells by blocking the activity of tyrosinase, an enzyme needed for the production of melanin. Working in cancer cells and in living zebrafish, Lee and her co-author Shin have further defined the molecular mechanism. They have demonstrated that glyceollins mediate their depigmentation activity through the action of ‘stem cell factor’, a growth factor needed for the development of melanocytes, and its downstream targets.