title: 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.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Chon
authors.affiliation: College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
authors.forename: Brandi
authors.initials: B
authors.lastname: Flanagan
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Lucas Campos
authors.initials: LC
authors.lastname: de Sá Rodrigues
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Piskun
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA; Institute for Clinical & Translational Research, University of Wisconsin-Madison, Madison, WI, USA; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: tjstein@wisc.edu.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Stein
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007211:Indoles / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000662:veterinary*; D010091:Oximes / Q000494:pharmacology*; D014158:Transcription, Genetic; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C483321:6-bromoindirubin-3'-oxime; D000970:Antineoplastic Agents; D007211:Indoles; D010091:Oximes; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: 6-Bromoindirubin-3′-oxime; Canine melanoma; Glycogen synthase kinase; Serine/threonine kinase; Wnt signaling