Docosahexaenoic acid inhibits melanin synthesis in murine melanoma cells in vitro through increasing tyrosinase degradation

Acta Pharmacol Sin. 2014 Apr;35(4):489-95. doi: 10.1038/aps.2013.174. Epub 2014 Feb 24.

Abstract

Aim: To investigate the effects of docosahexaenoic acid (DHA) on melanin synthesis and related regulatory mechanisms.

Methods: B16F10 mouse melanoma cells were exposed to DHA for 3 d, and melanin content and tyrosinase activity were measured. Western blot analysis was used to analyze the protein levels in DHA-mediated signal transduction pathways.

Results: DHA (1-25 μmol/L) did not affect the viability of B16F10 cells, but decreased α-MSH-induced melanin synthesis in a concentration-dependent manner. DHA concentration-dependently reduced tyrosinase activity in the cells, but did not affect mushroom tyrosinase activity in a cell-free system. Furthermore, DHA treatment significantly reduced tyrosinase level without affecting microphthalmia-associated transcription factor (MITF) in the cells. DHA did not activate ERK and Akt in the cells. Pretreatment with the proteasome inhibitor MG132 (80 nmol/L) abolished DHA-induced tyrosinase reduction.

Conclusion: DHA inhibits melanogenesis in B16F10 cells in vitro through increasing tyrosinase degradation. The results suggest that DHA may be a potential agent for treatment of hyperpigmentary disorders of skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Docosahexaenoic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Melanins / biosynthesis*
  • Melanoma, Experimental / enzymology*
  • Melanoma, Experimental / pathology
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Monophenol Monooxygenase / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors / pharmacology
  • Proteolysis
  • Signal Transduction / drug effects
  • Skin Neoplasms / enzymology*
  • Skin Neoplasms / pathology
  • Skin Pigmentation / drug effects
  • Time Factors
  • alpha-MSH / metabolism

Substances

  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Proteasome Inhibitors
  • Docosahexaenoic Acids
  • alpha-MSH
  • Monophenol Monooxygenase
  • Proteasome Endopeptidase Complex