Melatonin maximizes the therapeutic potential of non-preconditioned MSCs in a DEN-induced rat model of HCC - 17/05/19
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Graphical abstract |
Highlights |
• | Administration of melatonin before MSCs gave a better anti-HCC effect. |
• | This new treatment strategy significantly decreased tumor markers in serum. |
• | It also decreased number of glutathione S-transferase placental positive foci. |
• | It induced apoptosis and antioxidant enzymes but decreased MDA level in HCC. |
• | It also reduced inflammation, angiogenesis and metastasis in HCC. |
Abstract |
Pretreatment of mesenchymal stem cells (MSCs) with melatonin (Mel) improves their potential therapeutic effect on chronic diseases and cancers. However, this preconditioning strategy may direct the effect of Mel toward MSCs alone and deprive cancer cells of the oncostatic effect of Mel. Herein, we hypothesized that Mel given before transplantation of non-preconditioned MSCs may maximize the therapeutic outcome via the oncostatic effect of Mel by preparing a suitable tumor microenvironment for MSCs. Female rats (n = 60) were equally divided into 6 groups; normal control, diethylnitrosamine (DEN), DEN + Mel, DEN + MSCs, DEN + MSCs preconditioned with Mel, and DEN + MSCs + Mel. The obtained data revealed that administration of Mel before MSCs treatment without preconditioning yielded a better ameliorative effect against DEN-induced hepatocellular carcinoma (HCC) as evidenced by: 1) reduced serum levels of alpha fetoprotein and gamma-glutamyl transferase; 2) decreased number and area of glutathione S-transferase placental positive foci; 3) induced apoptosis (as indicated by increased cleaved caspase-3 activity, upregulated expression of proapoptotic genes Bax and caspase 3 and downregulated expression of anti-apoptotic genes Bcl2, survivin); 4) decreased malondialdehyde level and increased activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes; and 5) reduced inflammation, angiogenesis and metastasis as indicated by downregulated expression of interleukin 1 beta, nuclear factor kappa B, vascular endothelial growth factor, and matrix metallopeptidase 9 genes and upregulated expression of metalloproteinase inhibitor 1 gene. Thus, administration of Mel before MSCs (without preconditioning) fostered the survival and therapeutic potential of MSCs in HCC, possibly through induction of apoptosis and inhibition of inflammation and oxidative stress. This new strategy showed better therapeutic outcomes and may improve MSC-based therapies for HCC.
Le texte complet de cet article est disponible en PDF.Keywords : Melatonin, Mesenchymal stem cells, Hepatocellular carcinoma, Apoptosis, Oxidative stress
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Article 108732- juin 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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