Unraveling Novel Strategies in Mesothelioma Treatments Using a Newly Synthetized Platinum(IV) Compound
Cristina Favaron,
Ludovica Gaiaschi,
Claudio Casali,
Fabrizio De Luca,
Federica Gola,
Margherita Cavallo,
Valeria Ramundo,
Elisabetta Aldieri,
Gloria Milanesi,
Silvia Damiana Visonà,
Mauro Ravera,
Maria Grazia Bottone
Affiliations
Cristina Favaron
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
Ludovica Gaiaschi
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
Claudio Casali
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
Fabrizio De Luca
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
Federica Gola
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
Margherita Cavallo
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
Valeria Ramundo
Department of Oncology, University of Torino, Via Santena 5/bis, 10126 Torino, Italy
Elisabetta Aldieri
Department of Oncology, University of Torino, Via Santena 5/bis, 10126 Torino, Italy
Gloria Milanesi
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
Silvia Damiana Visonà
Unit of Legal Medicine and Forensic Sciences, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
Mauro Ravera
Department of Sciences and Technological Innovation (DiSIT), University of Piemonte Orientale “A. Avogadro”,Via Teresa Michel 11, 15121 Alessandria, Italy
Maria Grazia Bottone
Department of Biology and Biotechnology, University of Pavia, Via Ferrata 9, 27100 Pavia, Italy
Malignant mesothelioma is a rare tumor associated with asbestos exposure. Mesothelioma carcinogenesis is related to enhanced reactive oxygen species (ROS) production and iron overload. Despite the recent advances in biomedical sciences, to date the only available treatments include surgery in a small fraction of patients and platinum-based chemotherapy in combination with pemetrexed. In this view, the purpose of this study was to evaluate the therapeutic potential of the newly synthetized platinum prodrug Pt(IV)Ac-POA compared to cisplatin (CDDP) on human biphasic mesothelioma cell line MSTO-211H using different complementary techniques, such as flow-cytometry, transmission electron microscopy (TEM), and immunocytochemistry. Healthy mesothelial cell lines Met-5A were also employed to assess the cytotoxicity of the above-mentioned compounds. Our in vitro results showed that Pt(IV)Ac-POA significantly interfere with iron metabolisms and more importantly is able to trigger cell death, through different pathways, including ferroptosis, necroptosis, and apoptosis, in neoplastic cells. On the other hand, CDDP triggers mainly apoptotic and necrotic cell death. In conclusion, Pt(IV)Ac-POA may represent a new promising pharmacological agent in the treatment of malignant mesothelioma.
