ArticleCell metabolism2014
Inhibition of cancer cell proliferation by PPARγ is mediated by a metabolic switch that increases reactive oxygen species levels.
Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 128 citations in OpenAlex.
- ALDH18A1 silencing inhibits lung adenocarcinoma progression through mitochondrial dysfunction and PPAR signaling pathway activation.Biology direct · 2026Article
- Modulatory effects of Pioglitazone on the CAF-driven malignant phenotype in cervical cancer: an in vitro bidirectional study.Discover oncology · 2026Article
- PPAR-δ is a potential modulator of central carbon metabolism in human adipocytes.Bioinformation · 2026Article
- Pioglitazone modulates metabolic adaptation and peripheral nerve regeneration after injury.Molecular neurodegeneration · 2025Article
- PPARγ, a key modulator of metabolic reprogramming, stemness and chemoresistance associated with retrodifferentiation in human hepatocellular carcinomas.Cell death & disease · 2025Article
- Lipolysis gone rogue: the HSL connection in feeding cancer.Cell biology and toxicology · 2025Review
- The anti-diabetic PPARγ agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer.Molecular cancer · 2025Article
- Targeting PPARγ via SIAH1/2-mediated ubiquitin-proteasomal degradation as a new therapeutic approach in luminal-type bladder cancer.Cell death & disease · 2024Article
- Article
- Pan-cancer analysis reveals PDK family as potential indicators related to prognosis and immune infiltration.Scientific reports · 2024Article
- Molecular subtyping based on immune cell marker genes predicts prognosis and therapeutic response in patients with lung adenocarcinoma.BMC cancer · 2023Article
- NNAT is a novel mediator of oxidative stress that suppresses ER + breast cancer.Molecular medicine (Cambridge, Mass.) · 2023Article
- Metallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2023Article
- The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy.Frontiers in pharmacology · 2023Review
- Appraisal of the Possible Role of PPARPPAR research · 2023Article
- Pioglitazone and Prostate Cancer Risk in Taiwanese Male Patients with Type 2 Diabetes: A Retrospective Cohort Study.The world journal of men's health · 2023Article
- The Role of PPARs in Breast Cancer.Cells · 2022Review
- Transcriptional control of energy metabolism by nuclear receptors.Nature reviews. Molecular cell biology · 2022Review
- Review
- Metabolic Adaptation-Mediated Cancer Survival and Progression in Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The nuclear receptor peroxisome-proliferation-activated receptor gamma (PPARγ), a transcriptional master regulator of glucose and lipid metabolism, inhibits the growth of several common cancers, including lung cancer. In this study, we show that the mechanism by which activation of PPARγ inhibits proliferation of lung cancer cells is based on metabolic changes. We found that treatment with the PPARγ agonist pioglitazone triggers a metabolic switch that inhibits pyruvate oxidation and reduces glutathione levels. These PPARγ-induced metabolic changes result in a marked increase of reactive oxygen species (ROS) levels that lead to rapid hypophosphorylation of retinoblastoma protein (RB) and cell-cycle arrest. The antiproliferative effect of PPARγ activation can be prevented by suppressing pyruvate dehydrogenase kinase 4 (PDK4) or β-oxidation of fatty acids in vitro and in vivo. Our proposed mechanism also suggests that metabolic changes can rapidly and directly inhibit cell-cycle progression of cancer cells by altering ROS levels.
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