A New Platinum-Based Prodrug Candidate for Chemotherapy and Its Synergistic Effect With Hadrontherapy: Novel Strategy to Treat Glioblastoma

• DOI: 10.3389/fnins.2021.589906
• Publication Date: 2021-03-22T05:30:31Z
• Authors: Beatrice Ferrari; Elisa Roda; Erica Cecilia Priori; Fabrizio De Luca; Angelica Facoetti; Mauro Ravera; Federico Brandalise; Carlo Alessandro ...; Paola Rossi; Maria Grazia Bottone
• Keywords: Histone deacetylase inhibitor; HeLa

Glioblastoma (GBM) is the most common tumor of central nervous system. Current therapies, often associated with severe side effects, are inefficacious to contrast GBM relapsing forms. In trying overcome these drawbacks, ( OC -6-44)-acetatodiamminedichlorido(2-(2-propynyl)octanoato)platinum(IV), also called Pt(IV)Ac-POA, has been recently synthesized. This new prodrug bearing as axial ligand (2-propynyl)octanoic acid (POA), a histone deacetylase inhibitor, higher activity due (i) its high cellular accumulation by virtue lipophilicity and (ii) inhibition deacetylase, which leads increased exposure nuclear DNA, permitting platination promoting cancer cell death. present study, we investigated effects induced Pt(IV)Ac-POA potential antitumor in human U251 glioblastoma line using battery complementary techniques, i.e., flow cytometry, immunocytochemistry, TEM, Western blotting analyses. addition, synergistic effect innovative oncological hadrontherapy carbon ions was investigated, aim identify efficient anticancer treatment combination. Our vitro data demonstrated that able induce death, through different pathways, at concentrations lower than those tested for other platinum analogs. particular, an enduring effect, persisting long-term treatment, demonstrated. Interestingly, this further amplified combined ion radiation. conclusion, represents promising be incorporated into regimen GBM. Moreover, efficacy protocol chemotherapeutic followed radiation may represent approach, some typical limitations conventional therapeutic protocols treatment.