Collery, P.* ; Lagadec, P.* ; Krossa, I.* ; Cohen, C.* ; Antomarchi, J.* ; Varlet, D.* ; Lucio, M. ; Guigonis, J.M.* ; Scimeca, J.C.* ; Schmid-Antomarchi, H.* ; Schmid-Alliana, A.*
     
    
        
Relationship between the oxidative status and the tumor growth in transplanted triple-negative 4T1 breast tumor mice after oral administration of rhenium(I)-diselenoether.
    
    
        
    
    
        
        J. Trace Elem. Med. Biol. 71:126931 (2022)
    
    
    
      
      
	
	    Background: Selective inhibitory effects of rhenium(I)-diselenoether (Re-diSe) were observed in cultured breast malignant cells. They were attributed to a decrease in Reactive Oxygen Species (ROS) production. A concomitant decrease in the production of Transforming Growth Factor-beta (TGFβ1), Insulin Growth Factor 1 (IGF1), and Vascular Endothelial Growth Factor A (VEGFA) by the malignant cells was also observed. Aim: The study aimed to investigate the anti-tumor effects of Re-diSe on mice bearing 4T1 breast tumors, an experimental model of triple-negative breast cancer, and correlate them with several biomarkers. Material and methods: 4T1 mammary breast cancer cells were orthotopically inoculated into syngenic BALB/c Jack mice. Different doses of Re-diSe (1, 10, and 60 mg/kg) were administered orally for 23 consecutive days to assess the efficacy and toxicity. The oxidative status was evaluated by assaying Advanced Oxidative Protein Products (AOPP), and by the dinitrophenylhydrazone (DNPH) test in plasma of healthy mice, non-treated tumor-bearing mice (controls), treated tumor-bearing mice, and tumors in all tumor-bearing mice. Tumor necrosis factor (TNFα), VEGFA, VEGFB, TGFβ1, Interferon, and selenoprotein P (selenoP) were selected as biomarkers. Results: Doses of 1 and 10 mg/kg did not affect the tumor weights. There was a significant increase in the tumor weights in mice treated with the maximum dose of 60 mg/kg, concomitantly with a significant decrease in AOPP, TNFα, and TGFβ1 in the tumors. SelenoP concentrations increased in the plasma but not in the tumors. Conclusion: We did not confirm the anti-tumor activity of the Re-diSe compound in this experiment. However, the transplantation of the tumor cells did not induce an expected pro-oxidative status without any increase of the oxidative biomarkers in the plasma of controls compared to healthy mice. This condition could be essential to evaluate the effect of an antioxidant drug. The choice of the experimental model will be primordial to assess the effects of the Re-diSe compound in further studies.
	
	
	    
	
       
      
	
	    
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        Publication type
        Article: Journal article
    
 
    
        Document type
        Scientific Article
    
 
    
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        Keywords
        Aopp ; Breast Cancer ; Dnph Test ; Oxidative Status ; Rhenium ; Ros ; Selenium ; Selenoprotein P ; Tgfβ1 ; Tnfα ; Vegf
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2022
    
 
    
        Prepublished in Year
        0
    
 
    
        HGF-reported in Year
        2022
    
 
    
    
        ISSN (print) / ISBN
        0946-672X
    
 
    
        e-ISSN
        1878-3252
    
 
    
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	    Volume: 71,  
	    Issue: ,  
	    Pages: ,  
	    Article Number: 126931 
	    Supplement: ,  
	
    
 
    
        
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            Urban & Fischer
        
 
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30202 - Environmental Health
    
 
    
        Research field(s)
        Environmental Sciences
    
 
    
        PSP Element(s)
        G-504800-001
    
 
    
        Grants
        Agence de Développement Economique de la Corse
    
 
    
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        Erfassungsdatum
        2022-06-07