title: Investigation of the effects of deracoxib and piroxicam on the in vitro viability of osteosarcoma cells from dogs.
abstract: OBJECTIVE
  To determine whether exposure of canine osteosarcoma cells to deracoxib or piroxicam results in decreased viability, whether the cytotoxic effects of deracoxib and piroxicam involve induction of apoptosis, and whether deracoxib is a more potent inhibitor of osteosarcoma cell growth than piroxicam.
  
  
  METHODS
  1 fibroblast and 3 osteosarcoma cell lines.
  
  
  METHODS
  Cell counts and viability assays were performed using osteosarcoma cells (POS, highly metastatic POS, and canine osteosarcoma cell 31) and fibroblasts after 72 hours of incubation with deracoxib at concentrations of 0.5 microM to 500 microM or piroxicam at concentrations of 1 microM to 1,000 microM. Percentage viability was determined for each concentration. A DNA fragmentation analysis was performed to assess drug-induced apoptosis.
  
  
  RESULTS
  Concentration of deracoxib required for 50% inhibition of cell viability (IC50) was reached in all 3 osteosarcoma cell lines and ranged from 70 to 150 microM, whereas the IC50 for piroxicam was only reached in the POS cell line at 500 microM. Neither deracoxib nor piroxicam induced sufficient toxicity in fibroblasts to reach an IC50. Exposure of osteosarcoma cells to cytotoxic concentrations of deracoxib and piroxicam did not result in DNA fragmentation.
  
  
  CONCLUSIONS
  Intermediate and high concentrations of deracoxib and high concentrations of piroxicam were cytotoxic to osteosarcoma cells; neither drug inhibited cell viability at typical plasma concentrations in dogs. Deracoxib inhibited viability of cells at concentrations that did not affect fibroblast viability. There was no evidence of apoptosis induction for either drug; however, only 1 cell line was evaluated for apoptosis induction and only for a limited selection of drug concentrations.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610-0126, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Royals
authors.forename: James P
authors.initials: JP
authors.lastname: Farese
authors.forename: Rowan J
authors.initials: RJ
authors.lastname: Milner
authors.forename: Linda
authors.initials: L
authors.lastname: Lee-Ambrose
authors.forename: James
authors.initials: J
authors.lastname: van Gilder
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary*; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004587:Electrophoresis, Agar Gel / Q000662:veterinary; D005562:Formazans / Q000737:chemistry; D020128:Inhibitory Concentration 50; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary*; D010894:Piroxicam / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000737:chemistry; D000096926:Benzenesulfonamides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005562:Formazans; D010894:Piroxicam; D013449:Sulfonamides; D013778:Tetrazolium Salts; C079782:MTT formazan; C471996:deracoxib; D000096926:Benzenesulfonamides