title: Biologic activity of the novel small molecule STAT3 inhibitor LLL12 against canine osteosarcoma cell lines.
abstract: BACKGROUND
  STAT3 [1] has been shown to be dysregulated in nearly every major cancer, including osteosarcoma (OS). Constitutive activation of STAT3, via aberrant phosphorylation, leads to proliferation, cell survival and resistance to apoptosis. The present study sought to characterize the biologic activity of a novel allosteric STAT3 inhibitor, LLL12, in canine OS cell lines.
  
  
  RESULTS
  We evaluated the effects of LLL12 treatment on 4 canine OS cell lines and found that LLL12 inhibited proliferation, induced apoptosis, reduced STAT3 phosphorylation, and decreased the expression of several transcriptional targets of STAT3 in these cells. Lastly, LLL12 exhibited synergistic anti-proliferative activity with the chemotherapeutic doxorubicin in the OS lines.
  
  
  CONCLUSIONS
  LLL12 exhibits biologic activity against canine OS cell lines through inhibition of STAT3 related cellular functions supporting its potential use as a novel therapy for OS.
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jason I
authors.initials: JI
authors.lastname: Couto
authors.forename: Misty D
authors.initials: MD
authors.lastname: Bear
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
authors.forename: Michael
authors.initials: M
authors.lastname: Pennel
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Kulp
authors.forename: William C
authors.initials: WC
authors.lastname: Kisseberth
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: London
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000662:veterinary; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D010766:Phosphorylation / Q000187:drug effects; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; C549232:LLL12 compound; D050796:STAT3 Transcription Factor; D013449:Sulfonamides; D012313:RNA