title: Antagonism of serotonin receptor 1B decreases viability and promotes apoptosis in the COS canine osteosarcoma cell line.
abstract: Serotonin receptor 1B (5HTR1B) traditionally exhibits anti-proliferative activity in osteoblasts. We examined the expression and function of 5HTR1B in the COS canine osteosarcoma cell line and normal canine osteoblasts. Equal levels of 5HTR1B gene and protein expression were found between normal and malignant osteoblasts. Treatment with serotonin enhanced viability of osteosarcoma cells but not normal osteoblasts. Challenge with the 5HTR1B agonist anpirtoline caused no change in cell viability. Rather incubation with the specific receptor antagonist SB224289 caused reduction in osteoblast viability, with this effect more substantial in osteosarcoma cells. Investigation of this inhibitory activity showed 5HTR1B antagonism induces apoptosis in malignant cells. Evaluation of phosphorylated levels of CREB and ERK, transcriptional regulators associated with serotonin receptor signalling in osteoblasts, revealed aberrant 5HTR1B signalling in COS. Our results confirm the presence of 5HTR1B in a canine osteosarcoma cell line and highlight this receptor as a possible novel therapeutic target.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Viall
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Goodall
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: B
authors.initials: B
authors.lastname: Stang
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: K
authors.initials: K
authors.lastname: Marley
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Chappell
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bracha
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004283:Dog Diseases / Q000188:drug therapy / Q000378:metabolism*; D004285:Dogs; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000662:veterinary*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D010881:Piperidones / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*; D015398:Signal Transduction; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D013829:Thiadiazines / Q000494:pharmacology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D010880:Piperidines; D010881:Piperidones; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; C108518:SB 22489G; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013141:Spiro Compounds; D013829:Thiadiazines; D013654:Taurine; C075631:anpirtoline; D012701:Serotonin; C012566:taurolidine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 5HTR1B; bone; canine; osteoblast; osteosarcoma; serotonin