Métabolisme énergétique et traitements anticancéreux : caractérisation des effets de la Δ2-troglitazone et du 2-désoxyglucose sur les cellules d’adénocarcinomes mammaires

Abstract : The absence of response and the resistance of cancer cells to therapies are strong arguments for the development of new therapeutic strategies. Data from the literature suggest that it could be interesting to target energy metabolism of cancer cells. In this context, thiazolidinediones (TZDs) display antiproliferative effects that could be the result of energy metabolism alteration. During this PhD, we aimed at determining if Δ2-Troglitazone (Δ2-TGZ) could modify energy metabolism of breast cancer cells. The experiments performed previously used a culture medium containing 1% of fetal calf serum (FCS) that is rather a stress inducing condition that can disturb cell metabolism. Thus, we first characterized the effects of Δ2-TGZ in a 10% FCS containing medium. In this case, Δ2-TGZ still decreases cell proliferation of breast cancer cells, but it requires high doses. Besides, Δ2-TGZ induces cell cycle arrest instead of apoptosis. Then, we have shown that Δ2-TGZ induced modifications of energy metabolism, which are due to a decrease in oxidative phosphorylation. We also observed an increase in glycolytic activity that is probably a compensatory mechanism. During this part of our work, we have also characterized the mechanisms involved in the anticancer activity of 2-deoxyglucose. We have shown that in breast cancer cells, this compound acts not only by glycolysis inhibition but also by protein N-glycosylation alteration. We have now to determine the part of metabolic alterations that are involved in the anti-cancer effects of Δ2-TGZ
Document type :
Theses
File URL :
http://docnum.univ-lorraine.fr/public/DDOC_T_2017_0082_BERTHE.pdf
Complete list of metadatas

https://hal.univ-lorraine.fr/tel-01755224
Contributor : Thèses Ul <>
Submitted on : Thursday, July 12, 2018 - 9:28:00 AM
Last modification on : Thursday, July 12, 2018 - 1:37:19 PM
Long-term archiving on : Monday, October 15, 2018 - 1:16:05 PM

File

DDOC_T_2017_0082_BERTHE.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01755224, version 1

Citation

Audrey Berthe. Métabolisme énergétique et traitements anticancéreux : caractérisation des effets de la Δ2-troglitazone et du 2-désoxyglucose sur les cellules d’adénocarcinomes mammaires. Biologie cellulaire. Université de Lorraine, 2017. Français. ⟨NNT : 2017LORR0082⟩. ⟨tel-01755224⟩

Share

Metrics

Record views

332

Files downloads

712