Melanogenesis in uveal melanoma cells: Effect of argan oil

Int J Mol Med. 2017 Oct;40(4):1277-1284. doi: 10.3892/ijmm.2017.3104. Epub 2017 Aug 23.

Abstract

The mechanisms underlying cutaneous melanogenesis have been widely studied; however, very little is known about uveal melanogenesis. Melanin is normally produced by uveal melanocytes and gives the color to the iris. A derangement from this normal production may occur, for instance, by iatrogenic events, such as glaucoma therapy with prostaglandins that may enhance cutaneous and iris pigmentation. In this study, we investigated the mechanisms that regulate uveal melanogenesis in human uveal melanoma cells (92.1) and murine cutaneous melanoma cells (B16-F1). In the first part of the study, we compared the effects of known cutaneous pigmenting agents on the B16-F1 and 92.1 cells, showing an opposite response of the two cell lines. Subsequently, using argan oil, a known depigmenting agent for murine cutaneous melanoma cells, on 92.1 cells, we found that in these cells, it also functioned as an inhibitor of melanogenesis and tyrosinase expression. From a molecular perspective, treatment of the 92.1 cells with argan oil decreased melanogenesis-associated transcription factor (MITF) gene expression by inducing MITF phosphorylation at Ser73, thus leading to MITF ubiquitination and disposal. It also led to the downregulation of the extracellular signal-regulated kinase (ERK)1/2 and Akt pathways, also known to be involved in cutaneous melanogenesis, although with an opposing function. Taken together, our data indicate that: ⅰ) some differences exist in the regulation of melanogenesis between cutaneous and uveal melanoma cells; and ⅱ) argan oil exerts a depigmenting effect on 92.1 cells through its action on the ERK1/2 and Akt pathways.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Gene Expression Regulation
  • Humans
  • Melanins / antagonists & inhibitors*
  • Melanins / biosynthesis
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Melanocytes / pathology
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology
  • Mice
  • Microphthalmia-Associated Transcription Factor / genetics
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Organ Specificity
  • Phosphorylation / drug effects
  • Plant Oils / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Ubiquitination / drug effects
  • Uvea / drug effects*
  • Uvea / metabolism
  • Uvea / pathology
  • Uveal Neoplasms / drug therapy
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / metabolism
  • Uveal Neoplasms / pathology

Substances

  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Mitf protein, mouse
  • Plant Oils
  • argan oil
  • Monophenol Monooxygenase
  • Proto-Oncogene Proteins c-akt
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3

Supplementary concepts

  • Uveal melanoma