Indomethacin inhibits melanogenesis via down-regulation of Mitf mRNA transcription

Biosci Biotechnol Biochem. 2017 Dec;81(12):2307-2313. doi: 10.1080/09168451.2017.1394812. Epub 2017 Nov 1.

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) exhibit several divergent biological effects. In this study, we investigated the effect of indomethacin on melanin synthesis using B16F1 melanoma cells. Indomethacin inhibited α-melanocyte stimulating hormone (α-MSH)-enhanced melanin synthesis in a dose-dependent manner. Western blotting analysis revealed that indomethacin significantly suppressed tyrosinase and Mitf protein levels. In a luciferase reporter assay, we found that indomethacin reduced tyrosinase promoter activity. Moreover, real-time RT-PCR analysis showed that indomethacin lowered mRNA levels of melanogenic genes, including Mitf. Together, our findings indicate that indomethacin inhibits melanogenesis via the suppression of Mitf transcription.

Keywords: Mitf; indomethacin; melanogenesis; melanoma; tyrosinase.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects*
  • Indomethacin / pharmacology*
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Melanins / biosynthesis*
  • Melanoma, Experimental / pathology
  • Mice
  • Microphthalmia-Associated Transcription Factor / genetics*
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription, Genetic / drug effects

Substances

  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • RNA, Messenger
  • Monophenol Monooxygenase
  • Indomethacin