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Date publication
juillet 2014
Journal
International journal of oncology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SCHOHN Hervé
Tous les auteurs :
Huber S, Valente S, Chaimbault P, Schohn H
Lien Pubmed
Résumé
Thiazolidinediones have been shown to exhibit anti-proliferative effects against cancer cells derived from diverse tissue origins both in vivo and in vitro. We studied the anti-proliferative impact of 5-{4-(2-(5-ethyl-pyridin-2-yl)-ethoxy)-benzylidene}-thiazolidine-2,4-dione (∆2-pioglitazone), an analogue of pioglitazone, which binds to the nuclear peroxisome proliferator activated receptor-γ without activating it, on human adenocarcinoma-derived HT29 and HCT116 cells. In HTC116 cells, exposure to ∆2-pioglitazone reduced cell growth, but HT29 cells reached the plateau phase of growth after three days. ∆2-pioglitazone treatment did not trigger cells to enter apoptosis but enhanced the autophagy process. The effect of ∆2-pioglitazone treatment was related to the increase of oxygen and nitric oxide-derived species production and decreased glutathione content. Moreover, pre-treatment with an antioxidant before addition of ∆2-pioglitazone limited cell growth inhibition, reduced the production of reactive species and attenuated autophagy within the cells. The impact of the drug was associated with activation of the Nrf2/Keap1 pathway as demonstrated by the increased protein content of several antioxidant enzymes, notably heme-oxygenase-1.
Mots clés
Antineoplastic Agents, pharmacology, Autophagy, drug effects, Cell Proliferation, drug effects, Cell Survival, drug effects, Colonic Neoplasms, pathology, HCT116 Cells, HT29 Cells, Humans, Intracellular Signaling Peptides and Proteins, metabolism, Kelch-Like ECH-Associated Protein 1, NF-E2-Related Factor 2, metabolism, Pioglitazone, Signal Transduction, drug effects, Thiazolidinediones, pharmacology
Référence
Int. J. Oncol.. 2014 Jul;45(1):426-38
