Imidazole inhibits B16 melanoma cell migration via degradation of beta-catenin

J Pharm Pharmacol. 2010 Apr;62(4):491-6. doi: 10.1211/jpp.62.04.0012.

Abstract

Objectives: In the present study, we determined whether or not imidazole affects B16 murine melanoma cell migration to prevent melanoma metastasis.

Methods: To determine the effects of imidazole on melanoma cell migration, B16 cells were treated with imidazole at various concentrations, and the migration was measured using a scratch migration assay.

Key findings: Imidazole did not exhibit cytotoxic effects on B16 cells at a concentration below 100 microm. The anti-migratory activity of imidazole was determined by the scratch migration assay. Our results showed that imidazole significantly inhibits B16 cell migration. It is known that the Wnt/beta-catenin signalling pathway regulates the progression of melanocytic tumours and determines the prognosis in cutaneous melanomas. Western blot analysis demonstrated that imidazole increases phosphorylation of beta-catenin and subsequent degradation of beta-catenin. Moreover, inhibition of melanoma cell migration by imidazole was restored by MG132, a proteasome inhibitor, via inhibition of beta-catenin degradation.

Conclusions: Imidazole inhibits B16 cell migration through beta-catenin degradation, suggesting that imidazole is a potential candidate for the treatment of metastatic melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Leupeptins / pharmacology
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Mice
  • Phosphorylation
  • Signal Transduction / drug effects*
  • beta Catenin / metabolism*

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Leupeptins
  • beta Catenin
  • imidazole
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde