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


RESULTS
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.
Jeong
Yun-Mi
YM
Department of Biochemistry, Chung-Aug University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Korea.
Li
Hailan
H
Kim
Su Yeon
SY
Yun
Hye-Young
HY
Baek
Kwang Jin
KJ
Kwon
Nyoun Soo
NS
Kim
Dong-Seok
DS
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007976:Leupeptins / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism*
D000970:Antineoplastic Agents; D007093:Imidazoles; D007976:Leupeptins; D051176:beta Catenin; C029899:imidazole; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde