Identification des cibles moléculaires des composés de la famille des glycosides cardiaques

Abstract : Cardiac glycosides (CGs) are used in clinics to treat heart diseases. They inhibit the sodium-potassium-ATPase. Recently, anti-cancers activities have been ascribed to these compounds. In this study, we investigated the anti-cancer effects of UNBS1450, a compound partially modified from a CG extracted from the plant Calotropis procera. We analyzed its activities against a protein responsible for the chemoresistance of cancer cells: Mcl-1. We found that UNBS1450 decreases the levels of Mcl-1 in many forms of cancer, at very low concentrations. This modulation is important to induce cancer cell death and is common to other CGs. Furthermore, UNBS1450 also decreases the intracellular levels of another protein important for the cancer cell proliferation: c-Myc. This modulation takes place in the same conditions determining Mcl-1 decrease. Finally, we found UNBS1450 active on breast cancer, by blocking the cell cycle and proliferation of the breast cancer cells. In this study, we have shown that UNBS1450 and CGs in general induce cell death by decreasing the expression of Mcl-1 protein and affect cell proliferation with the concomitant decrease of c-Myc protein
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Submitted on : Thursday, March 29, 2018 - 1:12:36 PM
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Florian Muller. Identification des cibles moléculaires des composés de la famille des glycosides cardiaques. Biochimie, Biologie Moléculaire. Université de Lorraine, 2014. Français. ⟨NNT : 2014LORR0231⟩. ⟨tel-01751240⟩

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