title: Apoptotic effects of the tyrosine kinase inhibitor, masitinib mesylate, on canine osteosarcoma cells.
abstract: Osteosarcoma (OSA) is the most common primary bone tumor in dogs and the guarded prognosis highlights the necessity to find new treatments. Masitinib mesylate is a highly selective tyrosine kinase inhibitor that predominantly targets c-Kit and PDGFR-α/β. This study evaluated the in-vitro activity of masitinib against three canine OSA cell lines after treatment with increasing concentrations of masitinib (0.1-50 µmol/l) at 24, 48, and 72 h. The IC50 values at 72 h for the three OSA cell lines (POS, HMPOS, and COS31) were determined to be 11.04, 7.09, and 9.74 µmol/l, respectively. In addition, increases in caspase-3/7 activity and transferase dUTP nick end labeling-positive cells indicated apoptotic cell death. Because increased levels of vascular endothelial growth factor are found in dogs with OSA, vascular endothelial growth factor in the supernatant was quantified. Overall, the study found that masitinib causes dose-time dependent OSA cell death in vitro through initiation of caspase-mediated apoptosis, which supports future OSA clinical trials.
authors: Department of Small Animal Clinical Sciences, University of Florida, Gainesville, Florida 32610-0126, USA.
authors: Christine E
authors: CE
authors: Fahey
authors: Rowan J
authors: RJ
authors: Milner
authors: Kelvin
authors: K
authors: Kow
authors: Nicholas J
authors: NJ
authors: Bacon
authors: Marc E
authors: ME
authors: Salute
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines; D013844:Thiazoles / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; C526575:masitinib