title: 5-lipoxygenase expression and tepoxalin-induced cell death in squamous cell carcinomas in cats.
abstract: OBJECTIVE
  To assess expression pattern and subcellular compartmentalization of 5-lipoxygenase in cutaneous, UV radiation-induced, and oral squamous cell carcinomas (SCCs) in cats and determine the effects of cyclooxygenase or 5-lipoxygenase inhibition on proliferation or apoptosis in a feline oral squamous cell carcinoma (SCCF1) cell line.
  
  
  METHODS
  60 archived paraffin-embedded samples of SCCs from 60 cats and SCCF1 cells.
  
  
  METHODS
  Retrospective immunohistochemical analysis of the archived samples of SCCs (20 cutaneous, 20 UV radiation-induced, and 20 oral tumors) was performed. Cell culture proliferation assays involving SCCF1 cells were performed, and tepoxalin-induced apoptosis and signaling were examined via western blotting and annexin V staining.
  
  
  RESULTS
  Immunohistochemically, staining for 5-lipoxygenase was most frequently of greatest intensity in oral SCCs, whereas staining of cutaneous and UV radiation-induced lesions had less consistent 5-lipoxygenase expression. Exposure of SCCF1 cells to the 5-lipoxygenase inhibitor tepoxalin resulted in apoptosis; the effect appeared to be mediated via alteration of cell signaling rather than via suppression of lipid mediators that are typically produced as a result of 5-lipoxygenase activity.
  
  
  CONCLUSIONS
  In cats, expression of 5-lipoxygenase in SCCs appeared to differ depending on tumor location. The influence of tepoxalin-induced 5-lipoxygenase inhibition on a 5-lipoxygenase-expressing cell line coupled with the notable expression of 5-lipoxygenase in oral SCCs suggested that 5-lipoxygenase inhibition may have therapeutic benefits in affected cats. Although the safety of tepoxalin in cats has yet to be investigated, 5-lipoxygenase inhibitors should be evaluated for use as a potential treatment for SCCs in that species.
authors.affiliation: Departments of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. dr.joesh@gmail.com
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Wakshlag
authors.forename: Jeanine
authors.initials: J
authors.lastname: Peters-Kennedy
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Bushey
authors.forename: John P
authors.initials: JP
authors.lastname: Loftus
mesh_terms: D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D015153:Blotting, Western / Q000662:veterinary; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000503:physiopathology / Q000662:veterinary*; D002371:Cat Diseases / Q000201:enzymology* / Q000503:physiopathology*; D002415:Cats; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D007150:Immunohistochemistry / Q000662:veterinary; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009062:Mouth Neoplasms / Q000201:enzymology / Q000503:physiopathology / Q000662:veterinary*; D011720:Pyrazoles / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D017304:Annexin A5; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D001094:Arachidonate 5-Lipoxygenase; C073135:tepoxalin