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

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.

• Authors: Yun-Mi Jeong, Hailan Li, Su Yeon Kim, Hye-Young Yun, Kwang Jin Baek, Nyoun Soo Kwon, Dong-Seok Kim
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 62 Issue 4 Pg. 491-6 (Apr 2010) ISSN: 2042-7158 [Electronic] England
• PMID: 20604839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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