Chaetocin inhibits IBMX-induced melanogenesis in B16F10 mouse melanoma cells through activation of ERK

Chem Biol Interact. 2016 Feb 5:245:66-71. doi: 10.1016/j.cbi.2015.12.021. Epub 2015 Dec 31.

Abstract

Chaetocin is a natural product isolated from Chaetomium species that has anti-bacterial and anti-myeloma activities. In this study, we investigated the inhibitory effect of chaetocin on melanogenesis and the underlying mechanisms in B16F10 mouse melanoma cells. In the present study, chaetocin significantly inhibited IBMX-induced melanin production and tyrosinase activity without any cytotoxicity. Furthermore, chaetocin down-regulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine to melanin. We also observed that the protein level of MITF was significantly reduced by chaetocin treatment. In addition, we found that the anti-melanogenic effect of chaetocin was suppressed by treatment with the specific ERK inhibitor (PD98059). Accordingly, chaetocin inhibited melanogenesis via suppressing the protein level of MITF followed by activation of the ERK signaling pathway. These data suggest that chaetocin may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and a topical agent for treatment of hyperpigmentation disorders.

Keywords: Chaetocin; ERK; Extracellular signal-regulated kinases; Melanin; Microphthalmia-associated transcription factor; Tyrosinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine*
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Chaetomium / chemistry
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • MAP Kinase Signaling System / drug effects*
  • Melanins / genetics
  • Melanins / metabolism*
  • Melanoma, Experimental / chemically induced*
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism
  • Mice
  • Monophenol Monooxygenase / genetics
  • Monophenol Monooxygenase / metabolism
  • Piperazines / chemistry
  • Piperazines / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Melanins
  • Piperazines
  • chaetocin
  • Monophenol Monooxygenase
  • 1-Methyl-3-isobutylxanthine