Unraveling Novel Strategies in Mesothelioma Treatments Using a Newly Synthetized Platinum(IV) Compound

• Huvudupphovsmän: Cristina Favaron (Författare, medförfattare), Ludovica Gaiaschi (Författare, medförfattare), Claudio Casali (Författare, medförfattare), Fabrizio De Luca (Författare, medförfattare), Federica Gola (Författare, medförfattare), Margherita Cavallo (Författare, medförfattare), Valeria Ramundo (Författare, medförfattare), Elisabetta Aldieri (Författare, medförfattare), Gloria Milanesi (Författare, medförfattare), Silvia Damiana Visonà (Författare, medförfattare), Mauro Ravera (Författare, medförfattare), Maria Grazia Bottone (Författare, medförfattare)
• Materialtyp: Bok
• Publicerad: MDPI AG, 2024-07-01T00:00:00Z.
• Ämnen: article
• Länkar: Connect to this object online.
• Notes: 10.3390/pharmaceutics16081015; 1999-4923
• Keywords: malignant mesothelioma; iron metabolism; ferroptosis; programmed cell death; platinum (IV) chemotherapeutics; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 16, Iss 8, p 1015 (2024)

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.