title: Non-immunosuppressive FTY720-derivative OSU-2S mediates reactive oxygen species-mediated cytotoxicity in canine B-cell lymphoma.
abstract: OSU-2S is a FTY720 (Fingolimod) derivative that lacks immunosuppressive properties but exhibits strong anti-tumour activity in several haematological and solid tumour models. We have recently shown OSU-2S to mediate potent cytotoxicity in human mantle cell lymphoma cell lines and primary cells. We report here the pre-clinical activity of OSU-2S in spontaneous B-cell lymphoma of dogs which shares many characteristics of human lymphoma. OSU-2S mediated apoptosis in canine B-cell lines and primary B-cell lymphoma cells obtained from spontaneous lymphoma bearing dogs. OSU-2S induced reactive oxygen species (ROS) in canine lymphoma cells and inhibition of ROS partially rescued OSU-2S-mediated cell death. These studies provide a rational basis for the use of spontaneous lymphoma in pet dogs as a preclinical large animal model for the development of OSU-2S as small molecule for treating people and dogs with lymphoma.
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: R
authors.initials: R
authors.lastname: Mani
authors.affiliation: Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: R
authors.initials: R
authors.lastname: Yan
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors.forename: X
authors.initials: X
authors.lastname: Mo
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.|Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: C-S
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Phelps
authors.affiliation: Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: R
authors.initials: R
authors.lastname: Klisovic
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.|Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA.|Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Kisseberth
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.|Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: London
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.|Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: N
authors.initials: N
authors.lastname: Muthusamy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000662:veterinary*; D011409:Propylene Glycols / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C560545:OSU-2S; D011409:Propylene Glycols; D017382:Reactive Oxygen Species; D013110:Sphingosine
keywords: B-cell lymphoma; FTY720; OSU-2S; canine lymphoma; small molecule