title: Potent in vitro antiproliferative properties for a triplatinum cluster toward triple negative breast cancer cells.
abstract: The trinuclear platinum cluster [Pt3(μ-PBut2)3(CO)3]CF3SO3(I) was designed featuring the presence of a nearly equilateral platinum triangle bridged by three di-tert-butylphosphide ligands; in addition, each platinum center bears a terminal carbonyl ligand. This triplatinum cluster was initially developed in view of applications in the field of cluster-containing innovative materials. Yet, due to the large success of platinum complexes in cancer treatment, we also decided to explore its cytotoxic and anticancer properties. Accordingly, the solubility profile of this compound in several solvents was preliminarily investigated, revealing a conspicuous solubility in DMSO and DMSO/buffer mixtures; this makes the biological testing of I amenable. UV-Vis measurements showed that the triplatinum cluster is stable for several hours under a variety of conditions, within aqueous environments. No measurable reactivity was observed for I toward two typical model proteins, i.e. lysozyme and cytochrome c. On the contrary, a significant reactivity was evidenced when reacting I with small sulfur-containing ligands. In particular, a pronounced reactivity with reduced glutathione and cysteine emerged from ESI-MS experiments, proving complete formation of I-GSH and I-Cys derivatives, with the loss of a single carbonyl ligand. Starting from these encouraging results, the cytotoxic potential of I was assayed in vitro against a panel of representative cancer cell lines, and potent cytotoxic properties were disclosed. Of particular interest is the finding that the triplatinum species manifests potent antiproliferative properties toward Triple Negative Breast Cancer Cells, often refractory to most anticancer drugs. Owing to the reported encouraging results, a more extensive biological and pharmacological evaluation of this Pt cluster is now warranted to better elucidate its mode of action.
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, via Risorgimento 35, 56126 Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: alessandro.pratesi@unifi.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pratesi
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, via Risorgimento 35, 56126 Pisa, Italy.
authors.forename: Lorella
authors.initials: L
authors.lastname: Marchetti
authors.affiliation: School of Chemistry, Cardiff University, Main Building, Park place, Cardiff CF10 3AT, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, via Risorgimento 35, 56126 Pisa, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Leoni
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale G.B. Morgagni 50, Florence, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pillozzi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale G.B. Morgagni 50, Florence, Italy.
authors.forename: Olivia
authors.initials: O
authors.lastname: Crociani
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale G.B. Morgagni 50, Florence, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bartoli
authors.affiliation: Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: luigi.messori@unifi.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D018922:HL-60 Cells; D006801:Humans; D061986:MCF-7 Cells; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds
keywords: Cancer; Cytotoxicity; Mass spectrometry; Pt clusters