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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.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.

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

Mean weight of the mice after the inoculation of the cancer cells. Group 1: treatment by cisplatin (control); group 2: treatment with Re-diselenoether complex; group 3: treatment by Re-diselenoether complex + cisplatin
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Fig8: Mean weight of the mice after the inoculation of the cancer cells. Group 1: treatment by cisplatin (control); group 2: treatment with Re-diselenoether complex; group 3: treatment by Re-diselenoether complex + cisplatin

Mentions: There was no sign of clinical toxicity in all groups according to the body weight of the mice, as depicted in Fig. 8. There was a death, but one in each group, between days 26 and 39 before the injection of cisplatin, that could be probably attributed to the pulmonary metastases (an autopsy was performed in 2 mice, revealing a great number of metastases). Thus, the dose of 10 mg/kg/24 h of Re-diselenoether appeared to be well-tolerated.Fig. 8


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)

Mean weight of the mice after the inoculation of the cancer cells. Group 1: treatment by cisplatin (control); group 2: treatment with Re-diselenoether complex; group 3: treatment by Re-diselenoether complex + cisplatin
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig8: Mean weight of the mice after the inoculation of the cancer cells. Group 1: treatment by cisplatin (control); group 2: treatment with Re-diselenoether complex; group 3: treatment by Re-diselenoether complex + cisplatin
Mentions: There was no sign of clinical toxicity in all groups according to the body weight of the mice, as depicted in Fig. 8. There was a death, but one in each group, between days 26 and 39 before the injection of cisplatin, that could be probably attributed to the pulmonary metastases (an autopsy was performed in 2 mice, revealing a great number of metastases). Thus, the dose of 10 mg/kg/24 h of Re-diselenoether appeared to be well-tolerated.Fig. 8

Bottom Line: We now disclose an improved synthesis of this complex.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.

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