An Isoxazole Chalcone Derivative Enhances Melanogenesis in B16 Melanoma Cells via the Akt/GSK3β/β-Catenin Signaling Pathways

Molecules. 2017 Nov 28;22(12):2077. doi: 10.3390/molecules22122077.

Abstract

Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds, has become an interesting target for the development of anti-vitiligo agents. A series of novel isoxazole chalcone derivatives have been designed, synthesized, and evaluated for biological activities by our group. Among them, derivative 1-(4-((3-phenylisoxazol-5-yl)methoxy)phenyl)-3-phenylprop-2-en-1-one (PMPP) was identified as a potent tyrosinase activator with better activity and lower toxicity than the positive control 8-methoxypsoralen (8-MOP) in this study. Further investigations revealed that Akt and GSK3β were the signaling pathways involved in the hyperpigmentation of PMPP. Overall, these studies may provide a convenient and novel approach for the further development of anti-vitiligo agents.

Keywords: B16 melanoma; PI3K/Akt; Wnt/β-catenin; chalcone derivative; melanogenesis.

MeSH terms

  • Animals
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Melanins / biosynthesis*
  • Melanoma, Experimental
  • Mice
  • Monophenol Monooxygenase / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • beta Catenin / metabolism*

Substances

  • Chalcones
  • Melanins
  • Plant Extracts
  • beta Catenin
  • Monophenol Monooxygenase
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt