title: Fluoroquinolone-mediated inhibition of cell growth, S-G2/M cell cycle arrest, and apoptosis in canine osteosarcoma cell lines.
abstract: Despite significant advancements in osteosarcoma research, the overall survival of canine and human osteosarcoma patients has remained essentially static over the past 2 decades. Post-operative limb-spare infection has been associated with improved survival in both species, yet a mechanism for improved survival has not been clearly established. Given that the majority of canine osteosarcoma patients experiencing post-operative infections were treated with fluoroquinolone antibiotics, we hypothesized that fluoroquinolone antibiotics might directly inhibit the survival and proliferation of canine osteosarcoma cells. Ciprofloxacin or enrofloxacin were found to inhibit p21(WAF1) expression resulting in decreased proliferation and increased S-G(2)/M accumulation. Furthermore, fluoroquinolone exposure induced apoptosis of canine osteosarcoma cells as demonstrated by cleavage of caspase-3 and PARP, and activation of caspase-3/7. These results support further studies examining the potential impact of quinolones on survival and proliferation of osteosarcoma.
authors.affiliation: Department of Surgical and Radiological Sciences, University of California Davis School of Veterinary Medicine, Davis, California, United States of America.
authors.forename: Kyoung won
authors.initials: Kw
authors.lastname: Seo
authors.forename: Roseline
authors.initials: R
authors.lastname: Holt
authors.forename: Yong-Sam
authors.initials: YS
authors.lastname: Jung
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Rodriguez
authors.forename: Xinbin
authors.initials: X
authors.lastname: Chen
authors.forename: Robert B
authors.initials: RB
authors.lastname: Rebhun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004285:Dogs; D000077422:Enrofloxacin; D004789:Enzyme Activation / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D012516:Osteosarcoma / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D024841:Fluoroquinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases; D053148:Caspase 3; D053179:Caspase 7