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Evaluation of Delta 2-pioglitazone, an analogue of pioglitazone, on colon cancer cell survival: Evidence of drug treatment association with autophagy and activation of the Nrf2/Keap1 pathway

Abstract : 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-di one (Delta 2-pioglitazone), an analogue of pioglitazone, which binds to the nuclear peroxisome proliferator activated receptor-gamma without activating it, on human adenocarcinoma-derived HT29 and HCT116 cells. In HTC116 cells, exposure to Delta 2-pioglitazone reduced cell growth, but HT29 cells reached the plateau phase of growth after three days. Delta 2-pioglitazone treatment did not trigger cells to enter apoptosis but enhanced the autophagy process. The effect of Delta 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 Delta 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/Keapl pathway as demonstrated by the increased protein content of several antioxidant enzymes, notably heme-oxygenase-1.
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Submitted on : Thursday, March 23, 2017 - 2:04:19 PM
Last modification on : Monday, December 13, 2021 - 1:14:06 PM

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Sophie Huber, Sergio Valente, Patrick Chaimbault, Hervé Schohn. Evaluation of Delta 2-pioglitazone, an analogue of pioglitazone, on colon cancer cell survival: Evidence of drug treatment association with autophagy and activation of the Nrf2/Keap1 pathway. International Journal of Oncology, Spandidos Publications, 2014, 45 (1), pp.426-438. ⟨10.3892/ijo.2014.2408⟩. ⟨hal-01494415⟩

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