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6-Bromoindirubin-3'oxime (BIO) decreases proliferation and migration of canine melanoma cell lines.

Abstract
Despite recent therapeutic advances, malignant melanoma is an aggressive tumor in dogs and is associated with a poor outcome. Novel, targeted agents are necessary to improve survival. In this study, 6-bromoindirubin-3'-oxime (BIO), a serine/threonine kinase inhibitor with reported specificity for glycogen synthase kinase-3 beta (GSK-3β) inhibition, was evaluated in vitro in three canine melanoma cell lines (CML-10C2, UCDK9M2, and UCDK9M3) for β-catenin-mediated transcriptional activity, Axin2 gene and protein expression levels, cell proliferation, chemotoxicity, migration and invasion assays. BIO treatment of canine malignant melanoma cell lines at 5 µM for 72 h enhanced β-catenin-mediated transcriptional activity, suggesting GSK-3β inhibition, and reduced cell proliferation and migration. There were no significant effects on invasion, chemotoxicity, or apoptosis. The results suggest that serine/threonine kinases may be viable therapeutic targets for the treatment of canine malignant melanoma.
AuthorsEsther Chon, Brandi Flanagan, Lucas Campos de Sá Rodrigues, Caroline Piskun, Timothy J Stein
JournalVeterinary journal (London, England : 1997) (Vet J) Vol. 205 Issue 2 Pg. 305-12 (Aug 2015) ISSN: 1532-2971 [Electronic] England
PMID25130776 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • 6-bromoindirubin-3'-oxime
  • Antineoplastic Agents
  • Indoles
  • Oximes
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Cell Movement (drug effects)
  • Cell Proliferation (drug effects)
  • Dog Diseases (drug therapy)
  • Dogs
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Glycogen Synthase Kinase 3 (genetics, metabolism)
  • Glycogen Synthase Kinase 3 beta
  • Indoles (pharmacology)
  • Melanoma (drug therapy, veterinary)
  • Oximes (pharmacology)
  • Transcription, Genetic
  • beta Catenin (genetics, metabolism)

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