Downregulation of α-Melanocyte-Stimulating Hormone-Induced Activation of the Pax3-MITF-Tyrosinase Axis by Sorghum Ethanolic Extract in B16F10 Melanoma Cells

Int J Mol Sci. 2018 Jun 1;19(6):1640. doi: 10.3390/ijms19061640.

Abstract

Ultraviolet irradiation-induced hyperpigmentation of the skin is associated with excessive melanin production in melanocytes. Tyrosinase (TYR) is a key enzyme catalyzing the rate-limiting step in melanogenesis. TYR expression is controlled by microphthalmia-associated transcription factor (MITF) expression. Sorghum is a cereal crop widely used in a variety of foods worldwide. Sorghum contains many bioactive compounds and is beneficial to human health. However, the effects of sorghum in anti-melanogenesis have not been well characterized. In this study, the biological activity of sorghum ethanolic extract (SEE) on α-melanocyte-stimulating hormone (α-MSH)-induced TYR expression was evaluated in B16F10 melanoma cells. SEE attenuated α-MSH-induced TYR gene promoter activity through the downregulation of the transcription factor MITF. We found that paired box gene 3 (Pax3) contributes to the maximal induction of MITF gene promoter activity. Further analysis demonstrated that SEE inhibited α-MSH-induced Pax3 expression. The collective results indicate that SEE attenuates α-MSH-induced TYR expression through the suppression of Pax3-mediated MITF gene promoter activity. Targeting the Pax3-MITF axis pathway could be considered a potential strategy to increase the efficacy of anti-melanogenesis.

Keywords: melanogenesis; microphthalmia-associated transcription factor; paired box gene 3; sorghum; tyrosinase; α-melanocyte stimulating hormone.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Melanoma / drug therapy*
  • Melanoma / enzymology
  • Melanoma / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / genetics*
  • Monophenol Monooxygenase / metabolism
  • PAX3 Transcription Factor / metabolism
  • Plant Extracts / pharmacology*
  • Signal Transduction
  • Sorghum / chemistry*
  • alpha-MSH / metabolism*

Substances

  • Microphthalmia-Associated Transcription Factor
  • PAX3 Transcription Factor
  • Plant Extracts
  • Pax3 protein, mouse
  • alpha-MSH
  • Monophenol Monooxygenase