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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

a Light microscopy images (5x objective) and (b) Flow cytometry dot plots comparing MDA-MB231 cells that have been exposed or not to 10 μM of the Re-diselenoether complex for 48 h
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Fig3: a Light microscopy images (5x objective) and (b) Flow cytometry dot plots comparing MDA-MB231 cells that have been exposed or not to 10 μM of the Re-diselenoether complex for 48 h

Mentions: In the presence of a low concentration of Re (I)-diselenoether complex (10 μM), modifications in cell shape and morphology were clearly visible (Fig. 3a) when compared to untreated cells. These cellular alterations corresponded to a reduction in size and a loss of adherence indicating that treated cells were no longer proliferating and possibly included apoptotic cells. Further analysis was performed using Flow cytometry where Forward Scatter (FSC) and Side Scatter (SSC) parameters correspond to measurements of cell size (FSC) and granularity (SSC) (Fig. 3b). Cellular and nuclear debris generated by dead cells were characterized by low FSC/SSC values (<30 K) and excluded from the live gate. Upon 48 h exposure to Re, only 65.1 % of Re-treated cells were identified as alive compared to 92.1 % in the untreated condition. This heterogeneous population included cells of low FSC, indicative of non-proliferative cells, and cells of high SSC, indicative of granular apoptotic cells, which supported the microscopic observations (Fig. 3a).Fig 3


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)

a Light microscopy images (5x objective) and (b) Flow cytometry dot plots comparing MDA-MB231 cells that have been exposed or not to 10 μM of the Re-diselenoether complex for 48 h
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: a Light microscopy images (5x objective) and (b) Flow cytometry dot plots comparing MDA-MB231 cells that have been exposed or not to 10 μM of the Re-diselenoether complex for 48 h
Mentions: In the presence of a low concentration of Re (I)-diselenoether complex (10 μM), modifications in cell shape and morphology were clearly visible (Fig. 3a) when compared to untreated cells. These cellular alterations corresponded to a reduction in size and a loss of adherence indicating that treated cells were no longer proliferating and possibly included apoptotic cells. Further analysis was performed using Flow cytometry where Forward Scatter (FSC) and Side Scatter (SSC) parameters correspond to measurements of cell size (FSC) and granularity (SSC) (Fig. 3b). Cellular and nuclear debris generated by dead cells were characterized by low FSC/SSC values (<30 K) and excluded from the live gate. Upon 48 h exposure to Re, only 65.1 % of Re-treated cells were identified as alive compared to 92.1 % in the untreated condition. This heterogeneous population included cells of low FSC, indicative of non-proliferative cells, and cells of high SSC, indicative of granular apoptotic cells, which supported the microscopic observations (Fig. 3a).Fig 3

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