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

Collery P, Mohsen A, Kermagoret A, Corre S, Bastian G, Tomas A, Wei M, Santoni F, Guerra N, Desmaële D, d'Angelo J - Invest New Drugs (2015)

Bottom Line: We now disclose an improved synthesis of this complex.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.We have shown that Re-diselenoether gave both mono- and bis-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.

View Article: PubMed Central - PubMed

Affiliation: Société de Coordination de Recherches Thérapeutiques, Algajola, France, philippe.collery@gmail.com.

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 1 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-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.

No MeSH data available.


Related in: MedlinePlus

Imaging by bioluminescence in two mice (S1 and S2) treated by Re-diselenoether complex (from day 9 to day 36), on days 44 (11/03), 51 (18/03) and 58 (25/03)
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Fig6: Imaging by bioluminescence in two mice (S1 and S2) treated by Re-diselenoether complex (from day 9 to day 36), on days 44 (11/03), 51 (18/03) and 58 (25/03)

Mentions: The imaging by bioluminescence (Prof. Valérie Rouffiac, Institut Gustave Roussy, France) illustrated the effects of Re (I)-diselenoether complex on the tumor activity (Fig. 6). In the group of the two mice (S1 and S2) treated with the Re drug, the tumor was visible on the first imaging on day 44 after the inoculation of the cancer cells (S1-S2, 11/03 images). On day 51 (18/03), the tumor has disappeared in mouse S2. On day 58 (25/03), there was no detectable tumor in the two mice, indicating a complete regression of the tumor activity, an effect sustained a long time after the interruption of the treatment with the Re-diselenoether complex (end of the treatment on day 36 after the inoculation of the cancer cells).Fig. 6


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

Collery P, Mohsen A, Kermagoret A, Corre S, Bastian G, Tomas A, Wei M, Santoni F, Guerra N, Desmaële D, d'Angelo J - Invest New Drugs (2015)

Imaging by bioluminescence in two mice (S1 and S2) treated by Re-diselenoether complex (from day 9 to day 36), on days 44 (11/03), 51 (18/03) and 58 (25/03)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491361&req=5

Fig6: Imaging by bioluminescence in two mice (S1 and S2) treated by Re-diselenoether complex (from day 9 to day 36), on days 44 (11/03), 51 (18/03) and 58 (25/03)
Mentions: The imaging by bioluminescence (Prof. Valérie Rouffiac, Institut Gustave Roussy, France) illustrated the effects of Re (I)-diselenoether complex on the tumor activity (Fig. 6). In the group of the two mice (S1 and S2) treated with the Re drug, the tumor was visible on the first imaging on day 44 after the inoculation of the cancer cells (S1-S2, 11/03 images). On day 51 (18/03), the tumor has disappeared in mouse S2. On day 58 (25/03), there was no detectable tumor in the two mice, indicating a complete regression of the tumor activity, an effect sustained a long time after the interruption of the treatment with the Re-diselenoether complex (end of the treatment on day 36 after the inoculation of the cancer cells).Fig. 6

Bottom Line: We now disclose an improved synthesis of this complex.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.We have shown that Re-diselenoether gave both mono- and bis-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.

View Article: PubMed Central - PubMed

Affiliation: Société de Coordination de Recherches Thérapeutiques, Algajola, France, philippe.collery@gmail.com.

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 1 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-guanine Re adducts, the species assumed to be responsible for the DNA intrastrand lesions.

No MeSH data available.


Related in: MedlinePlus