title: Investigation of the cytotoxic effect of flavopiridol in canine lymphoma cell lines.
abstract: The cyclin-dependent kinase (CDK) inhibitor, flavopiridol, was tested as a potential new cancer therapeutic agent to treat canine lymphoma by examining its effect on cell growth of canine lymphoma cell lines in vitro. Flavopiridol induced profound cell death in all eight lymphoma cell lines at 400 nM, and in all cases cell death was due to apoptosis. Apoptosis was inhibited by caspase inhibitor, despite the variable sensitivities between cell lines. Analysis of the mechanism of flavopiridol-induced apoptosis showed that Rb phosphorylation was inhibited, possibly due to CDK4 or CDK6 inhibition. There was also decreased expression of Rb protein and anti-apoptotic proteins, Mcl-1 and XIAP, possibly through transcriptional regulation by inhibition of CDK7 or CDK9 activation. Canine lymphoma cell line-xenotransplanted mice were then treated with flavopiridol and profound tumour shrinkage was observed. This study describes a new therapeutic approach using flavopiridol for canine lymphoma treatment.
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ema
authors.affiliation: Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Igase
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yanase
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Umeki
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hiraoka
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.|Biomedical Science Center for Translational Research, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Okuda
authors.affiliation: Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.|Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.|Biomedical Science Center for Translational Research, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western / Q000662:veterinary; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000187:drug effects; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology*; D004285:Dogs; D005419:Flavonoids / Q000494:pharmacology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D051379:Mice; D016688:Mice, Inbred NOD; D010880:Piperidines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D018844:Cyclin-Dependent Kinases
keywords: apoptosis; canine; cyclin-dependent kinase; flavopiridol; lymphoma