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Etude des réponses du métabolisme de Dunaliella sp au stress abiotique pour une exploitation en thérapie : analyses génomiques et protéomiques

Abstract : In this work, we optimized the culture conditions of Dunaliella salina sp, isolated from the Tunisian coast to increase carotenoids production. For that, we performed a Box-Behnken experimental design to study the effects and interactions between salinity, light intensity and nitrogen supply conditions. We succeeded to improve the intracellular production of carotenoids by five-fold. Subsequently, we studied the characteristics of cultured cells under stress (DSS) and control (DSC) conditions as well as the transcriptional modifications of the genes involved in stress response and β-carotene synthesis. Amongst studied genes, Lycopene β cyclase gene (LCYB) and Carotene globular protein gene (Cgp) were significantly overexpressed. 3D structures of the corresponding proteins and their posttranslational modifications have been determined. The anticancer activity of this strain cultivated under normal (DSC) or stressed (DSS) conditions was explored showing that the aqueous extract of DSS was four times more toxic than DSC one against murine breast cancer 4T1 cells. The extract was also active against A549 human lung adenocarcinoma cells and human Hela cells of cervical cancer. The study of the genomic DNA fragmentation of the treated 4T1 cells indicates that the extract induces an apoptosis cell death. Validation of these results by Western Blot was also performed by proving the activation of caspases 3 and 9 and the deactivation of PARP-1. In vivo experiments were performed on Balb/c mice that have been orthotopically implanted with 4T1 cells into the mammary glands. The results show a delay of the tumor growth and a decrease of the tumor size in mice treated with DSS aqueous extract. Interestingly, an activation of the anti-cancer immunity was observed with an increase of Natural Killer cells, activated cytotoxic lymphocytes and plasmacytoid DC as well as repression of immunosuppressive myeloid cells and enzymes (Arg-1, NOS-2 and COX-2). Altogether, our data reveal the potentiality of D. salina aqueous extract grown under stressed conditions as anti-cancer agent, which deserves attention in the future.
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Submitted on : Friday, June 24, 2022 - 4:24:16 PM
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Fatma Elleuch. Etude des réponses du métabolisme de Dunaliella sp au stress abiotique pour une exploitation en thérapie : analyses génomiques et protéomiques. Organisation et fonctions cellulaires [q-bio.SC]. Université d'Orléans; École nationale d'ingénieurs de Sfax (Tunisie), 2019. Français. ⟨NNT : 2019ORLE3128⟩. ⟨tel-03704190⟩

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