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Potent in vitro antiproliferative properties for a triplatinum cluster toward triple negative breast cancer cells

Gabbiani, Chiara, Pratesi, Alessandro, Marchetti, Lorella, Casini, Angela, Leoni, Piero, Pillozzi, Serena, Crociani, Olivia, Bartoli, Gianluca and Messori, Luigi 2016. Potent in vitro antiproliferative properties for a triplatinum cluster toward triple negative breast cancer cells. Journal of Inorganic Biochemistry 163 , pp. 318-322. 10.1016/j.jinorgbio.2016.06.024

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Subjects: Q Science > QD Chemistry
Uncontrolled Keywords: Pt clusters; Cytotoxicity; Mass spectrometry; Cancer
Additional Information: This journal has an embargo period of 24 months - https://www.elsevier.com/journals/journal-of-inorganic-biochemistry/0162-0134/open-access-options (accessed 15.7.16).
Publisher: Elsevier
ISSN: 0162-0134
Date of First Compliant Deposit: 15 July 2016
Date of Acceptance: 23 June 2016
Last Modified: 09 Jul 2017 16:11
URI: http://orca.cf.ac.uk/id/eprint/92751

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