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Journal Articles Investigational New Drugs Year : 2015

Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer

Abstract

Rhenium (I)-diselenother (Re-diselenoether) is a water soluble metal-based compound, combining one atom of rhenium and two atoms of selenium. This compound has been reported to exhibit marked activities against several solid tumor cell lines. We now disclose an improved synthesis of this complex. The Re-diselenoether showed a potent inhibitory effect on MDA-MB231 cell division in vitro, which lasted when the complex was no longer present in the culture. Re-diselenoether induced a remarkable reduction of the volume of the primitive breast tumors and of the pulmonary metastases without clinical signs of toxicity, in mice-bearing a MDA-MB231 Luc+ tumor, orthotopically transplanted, after a daily oral administration at the dose of 10 mg/kg/d. Interestingly, an antagonism was observed when cisplatin was administered as a single i.p. injection one week after the end of the Re-diselenoether administration. In an effort to gain insight of the mechanisms of action of Re-diselenoether complex, interaction with 9-methylguanine as a nucleic acid base model was studied. We have shown that Re-diselenoether gave both mono-and bis-Re-guanine adducts, the species assumed to be responsible for the DNA intrastrand lesion.
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Dates and versions

hal-01346417 , version 1 (18-07-2016)

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Philippe Collery, Ahmed Mohsen, Anthony Kermagoret, Samantha Corre, Gérard Bastian, et al.. Antitumor activity of a rhenium (I)-diselenoether complex in experimental models of human breast cancer. Investigational New Drugs, 2015, Investigational New Drugs, 33 (4), pp.848-860. ⟨10.1007/s10637-015-0265-z⟩. ⟨hal-01346417⟩
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