title: Reduced cell viability and apoptosis induction in human thyroid carcinoma and mesothelioma cells exposed to cidofovir.
abstract: Besides its well-recognized antiviral activity, Cidofovir (CDV) has been shown to exert anticancer properties both within in vitro and in vivo models. The aim of this study was to evaluate the effects of CDV on still unexplored cultured cancer cells from human mesothelioma as well as breast, colon, liver, lung, prostate, and thyroid carcinomas. Overall, a dose- and time-dependent inhibition of cell viability was observed after CDV exposure. To clarify the mechanisms underlying CDV action, apoptotic cell death was investigated in two infected cell lines [Ist-Mes1 and Ist-Mes2 mesothelioma cells (SV40+)] and in two uninfected cell lines (NCI-H2425 mesothelioma cells and FTC-133 thyroid cancer cells), which resulted the most sensitive to CDV treatment. Reduced expression of procaspase-3 and increased expression of PARP p85 fragment were observed in both infected and uninfected mesothelioma cells, indicating apoptosis induction by CDV in a virus-independent manner. Similarly, the increase of the pro-apoptotic proteins p53, cytochrome c and caspase-3, the decrease of the survival protein Bcl-x, and the increment of Bax/Bcl-2 ratio revealed the occurrence of apoptosis in CDV-treated FTC-133. The presence of nuclear DNA fragmentation confirmed apoptotic cell death by CDV. Overall, our findings warrant further investigations to explore the therapeutic potential of CDV for human mesothelioma and follicular thyroid carcinoma.
authors.affiliation: Section of Clinical Biochemistry and Molecular Genetics, Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Catalani
authors.affiliation: Section of Clinical Biochemistry and Molecular Genetics, Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Palma
authors.affiliation: Section of Clinical Biochemistry and Molecular Genetics, Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Italy.
authors.forename: Serafina
authors.initials: S
authors.lastname: Battistelli
authors.affiliation: Preclinical Models and New Therapeutic Agent Unit, Translational Research Functional Departmental Area, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nuvoli
authors.affiliation: Preclinical Models and New Therapeutic Agent Unit, Translational Research Functional Departmental Area, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Galati
authors.affiliation: Section of Clinical Biochemistry and Molecular Genetics, Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Italy. Electronic address: serena.benedetti@uniurb.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Benedetti
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy / Q000821:virology; D063065:Organophosphonates / Q000494:pharmacology*; D030361:Papillomavirus Infections; D027601:Polyomavirus Infections; D013964:Thyroid Neoplasms / Q000188:drug therapy; D014412:Tumor Virus Infections; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000821:virology
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir
keywords: Apoptosis induction; Cancer cells; Cidofovir; Mesothelioma; Thyroid carcinoma