| Autor: |
Dell'Anno I; Genetic Unit, Department of Biology, University of Pisa, 56126 Pisa, Italy., Melani A; Genetic Unit, Department of Biology, University of Pisa, 56126 Pisa, Italy., Martin SA; Centre for Cancer Cell and Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK., Barbarino M; Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.; Translational Oncology, Center for Biotechnology, College of Science and Technology, Temple University, Sbarro Institute for Cancer Research and Molecular Medicine, Philadelphia, PA 19122, USA., Silvestri R; Genetic Unit, Department of Biology, University of Pisa, 56126 Pisa, Italy., Cipollini M; Genetic Unit, Department of Biology, University of Pisa, 56126 Pisa, Italy., Giordano A; Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.; Translational Oncology, Center for Biotechnology, College of Science and Technology, Temple University, Sbarro Institute for Cancer Research and Molecular Medicine, Philadelphia, PA 19122, USA., Mutti L; Translational Oncology, Center for Biotechnology, College of Science and Technology, Temple University, Sbarro Institute for Cancer Research and Molecular Medicine, Philadelphia, PA 19122, USA., Nicolini A; Department of Oncology, Transplantations and New Technologies in Medicine, University of Pisa, 56126 Pisa, Italy., Luzzi L; Department of Medicine, Surgery and Neurosciences, Siena University Hospital, 53100 Siena, Italy., Aiello R; Toma Institute Srl, Via Cesare Rosaroll 24, 80139 Napoli, Italy., Gemignani F; Genetic Unit, Department of Biology, University of Pisa, 56126 Pisa, Italy., Landi S; Genetic Unit, Department of Biology, University of Pisa, 56126 Pisa, Italy. |
| Abstrakt: |
The lack of effective therapies remains one of the main challenges for malignant pleural mesothelioma (MPM). In this perspective, drug repositioning could accelerate the identification of novel treatments. We screened 1170 FDA-approved drugs on a SV40-immortalized mesothelial (MeT-5A) and five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) cell lines. Biological assays were carried out for 41 drugs, showing the highest cytotoxicity and for whom there were a complete lack of published literature in MPM. Cytotoxicity and caspase activation were evaluated with commercially available kits and cell proliferation was assayed using MTT assay and by clonogenic activity with standard protocols. Moreover, the five most effective drugs were further evaluated on patient-derived primary MPM cell lines. The most active molecules were cephalomannine, ouabain, alexidine, thonzonium bromide, and emetine. Except for alexidine, these drugs inhibited the clonogenic ability and caspase activation in all cancer lines tested. The proliferation was inhibited also on an extended panel of cell lines, including primary MPM cells. Thus, we suggest that cephalomannine, ouabain, thonzonium bromide, and emetine could represent novel candidates to be repurposed for improving the arsenal of therapeutic weapons in the fight against MPM. |
