Cajanin Suppresses Melanin Synthesis through Modulating MITF in Human Melanin-Producing Cells

Molecules. 2021 Oct 5;26(19):6040. doi: 10.3390/molecules26196040.

Abstract

Despite its classification as a non-life-threatening disease, increased skin pigmentation adversely affects quality of life and leads to loss of self-confidence. Until now, there are no recommended remedies with high efficacy and human safety for hyperpigmentation. This study aimed to investigate anti-melanogenic activity and underlying mechanism of cajanin, an isoflavonoid extracted from Dalbergia parviflora Roxb. (Leguminosae) in human melanin-producing cells. Culture with 50 μM cajanin for 48-72 h significantly suppressed proliferation in human melanoma MNT1 cells assessed via MTT viability assay. Interestingly, cajanin also efficiently diminished melanin content in MNT1 cells with the half maximum inhibitory concentration (IC50) at 77.47 ± 9.28 μM. Instead of direct inactivating enzymatic function of human tyrosinase, down-regulated mRNA and protein expression levels of MITF and downstream melanogenic enzymes, including tyrosinase, TRP-1 and Dct (TRP-2) were observed in MNT1 cells treated with 50 μM cajanin for 24-72 h. Correspondingly, treatment with cajanin modulated the signaling pathway of CREB and ERK which both regulate MITF expression level. Targeted suppression on MITF-related proteins in human melanin-producing cells strengthens the potential development of cajanin as an effective treatment for human hyperpigmented disorders.

Keywords: Dalbergia parviflora; human melanocyte; hyperpigmentation; tyrosinase.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dalbergia / chemistry
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperpigmentation / drug therapy
  • Interferon Type I / metabolism
  • Intramolecular Oxidoreductases / metabolism
  • Isoflavones / chemistry
  • Isoflavones / pharmacology*
  • Melanins / biosynthesis
  • Melanocytes / drug effects
  • Melanocytes / enzymology
  • Melanocytes / metabolism
  • Melanoma / drug therapy*
  • Melanoma / enzymology
  • Melanoma / metabolism*
  • Microphthalmia-Associated Transcription Factor / drug effects*
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Monophenol Monooxygenase / metabolism
  • Plant Extracts / pharmacology
  • Pregnancy Proteins / metabolism
  • Quality of Life
  • Signal Transduction / drug effects*

Substances

  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Interferon Type I
  • Isoflavones
  • MITF protein, human
  • Melanins
  • Microphthalmia-Associated Transcription Factor
  • Plant Extracts
  • Pregnancy Proteins
  • interferon tau
  • Monophenol Monooxygenase
  • Extracellular Signal-Regulated MAP Kinases
  • Intramolecular Oxidoreductases
  • dopachrome isomerase