Resveratrol-mediated inhibition of cyclooxygenase-2 in melanocytes suppresses melanogenesis through extracellular signal-regulated kinase 1/2 and phosphoinositide 3-kinase/Akt signalling

Eur J Pharmacol. 2019 Oct 5:860:172586. doi: 10.1016/j.ejphar.2019.172586. Epub 2019 Aug 1.

Abstract

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), has been reported to exert a variety of important pharmacological effects including anti-inflammatory, anticancer, and direct inhibition of tyrosinase. This study aimed to examine the expression of melanogenic molecules following down-regulation of cyclooxygenase (COX)-2 expression by resveratrol and the related signal transduction pathways in mouse B16F10 melanoma cells and zebrafish larvae. We report that resveratrol suppressed COX-2 in melanocytes and decreased the expressions of tyrosinase and microphthalmia-associated transcription factor (MITF). Furthermore, inhibition of COX-2 with NS398 enhanced resveratrol-reduced tyrosinase and MITF expression. Resveratrol also induced phosphorylation of extracellular signal-regulated 1/2 (ERK1/2) and phosphoinositide-3 (PI-3)-kinase/Akt. Inhibition of ERK1/2 or PI-3K/Akt by PD98059 and LY294002 restored the decreased tyrosinase activity and MITF expression via resveratrol-mediated down-regulation of COX-2. Additionally, resveratrol inhibited body pigmentation in zebrafish. These results indicated that resveratrol inhibited melanogenesis by down-regulating COX-2 via ERK1/2 and PI-3K/Akt pathways in B16F10 cells.

Keywords: B16F10; COX-2; MITF; Resveratrol; Tyrosinase; Zebrafish.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Melanins / biosynthesis*
  • Melanocytes / cytology
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Resveratrol / pharmacology*
  • Signal Transduction / drug effects*

Substances

  • Cyclooxygenase 2 Inhibitors
  • Melanins
  • Cyclooxygenase 2
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Resveratrol