Potent in vitro antiproliferative properties for a triplatinum cluster toward triple negative breast cancer cells
Autor: | Lorella Marchetti, Angela Casini, Gianluca Bartoli, Luigi Messori, Piero Leoni, Olivia Crociani, Chiara Gabbiani, Alessandro Pratesi, Serena Pillozzi |
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Rok vydání: | 2016 |
Předmět: |
Organoplatinum Compounds
Stereochemistry Cytotoxicity chemistry.chemical_element Antineoplastic Agents Breast Neoplasms HL-60 Cells 010402 general chemistry 01 natural sciences Biochemistry Inorganic Chemistry Humans QD Reactivity (chemistry) Solubility Mode of action Cancer Mass spectrometry 010405 organic chemistry Ligand Pt clusters In vitro 0104 chemical sciences chemistry MCF-7 Cells Female Drug Screening Assays Antitumor Platinum Cysteine |
Zdroj: | Journal of Inorganic Biochemistry. 163:318-322 |
ISSN: | 0162-0134 |
DOI: | 10.1016/j.jinorgbio.2016.06.024 |
Popis: | 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. |
Databáze: | OpenAIRE |
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