title: Cytotoxic effects induced by interferon-ω gene lipofection through ROS generation and mitochondrial membrane potential disruption in feline mammary carcinoma cells.
abstract: Progress in comparative oncology promises advances in clinical cancer treatments for both companion animals and humans. In this context, feline mammary carcinoma (FMC) cells have been proposed as a suitable model to study human breast cancer. Based on our previous data about the advantages of using type I interferon gene therapy over the respective recombinant DNA derived protein, the present work explored the effects of feline interferon-ω gene (fIFNω) transfer on FMC cells. Three different cell variants derived from a single spontaneous highly aggressive FMC tumor were successfully established and characterized. Lipofection of the fIFNω gene displayed a significant cytotoxic effect on the three cell variants. The extent of the response was proportional to ROS generation, mitochondrial membrane potential disruption and calcium uptake. Moreover, a lower sensitivity to the treatment correlated with a higher malignant phenotype. Our results suggest that fIFNω lipofection could offer an alternative approach in veterinary oncology with equal or superior outcome and with less adverse effects than recombinant fIFNω therapy.
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Av. San Martín 5481, 1417 Buenos Aires, Argentina.
authors.forename: Marcela Solange
authors.initials: MS
authors.lastname: Villaverde
authors.affiliation: Instituto de Nanobiotecnología (NANOBIOTEC, CONICET-UBA), Cátedra de Microbiología Industrial y Biotecnología, Facultad de Farmacia y Bioquímica (UBA), Junín 956, 1113 Buenos Aires, Argentina.
authors.forename: Alexandra Marisa
authors.initials: AM
authors.lastname: Targovnik
authors.affiliation: Instituto de Nanobiotecnología (NANOBIOTEC, CONICET-UBA), Cátedra de Microbiología Industrial y Biotecnología, Facultad de Farmacia y Bioquímica (UBA), Junín 956, 1113 Buenos Aires, Argentina.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Miranda
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Av. San Martín 5481, 1417 Buenos Aires, Argentina.
authors.forename: Liliana María Elena
authors.initials: LM
authors.lastname: Finocchiaro
authors.affiliation: Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Av. San Martín 5481, 1417 Buenos Aires, Argentina. Electronic address: gglikin@bg.fcen.uba.ar.
authors.forename: Gerardo Claudio
authors.initials: GC
authors.lastname: Glikin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D045744:Cell Line, Tumor; D005260:Female; D007370:Interferon Type I / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D017382:Reactive Oxygen Species; C063743:interferon omega 1; D002118:Calcium
keywords: Feline interferon-omega; Feline mammary carcinoma; Plasmid lipofection; ROS