ArticleAmerican journal of physiology. Cell physiology2015
PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.
Article in American journal of physiology. Cell physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 58 citations in OpenAlex.
- Serum Concentrations of Per- and Polyfluoroalkyl Substances and Risk of Renal Cell Carcinoma.Journal of the National Cancer Institute · 2021Trial
- Neurexophilin 4 facilitates the malignant progression of kidney renal clear cell carcinoma by regulating PI3K/AKT-mediated glycolysis.Molecular genetics and genomics : MGG · 2026Article
- Metabolic reprogramming-mediated therapeutic resistance in renal cell carcinoma: Mechanisms and targeted intervention strategies.iScience · 2026Review
- Tubular ACSM3 controls fatty acid metabolism and safeguards against acute kidney injury in male mice.Nature communications · 2026Article
- Cannabigerol and Cannabichromene Induce Lung Cancer Cell Death and Apoptosis-Contribution of PPARα to Cannabigerol Effects.Antioxidants (Basel, Switzerland) · 2026Article
- Mitochondrial Dysfunction in Renal Cell Carcinoma: A Comprehensive Review of Pathogenic Mechanisms and Emerging Therapeutic Opportunities.Oncology research · 2026Review
- The Function of PPARα in Cancer Drug Development: A Promising Target for Cancer Treatment.Current cancer drug targets · 2026Review
- Pharmacological inhibition of Peroxisome Proliferation-Activated Receptor Delta (PPARδ) imparts selective leukemia cell death.Cancer & metabolism · 2025Article
- Machine learning-derived prognostic signature integrating programmed cell death and mitochondrial function in renal clear cell carcinoma: identification of PIF1 as a novel target.Cancer immunology, immunotherapy : CII · 2025Article
- Comprehensive analysis of PSMG3 in pan-cancer and validation of its role in hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Involvement of per- and polyfluoroalkyl compounds in tumor development.Archives of toxicology · 2024Review
- Case-Cohort Study of the Association between PFAS and Selected Cancers among Participants in the American Cancer Society's Cancer Prevention Study II LifeLink Cohort.Environmental health perspectives · 2023Article
- Proanthocyanidin Alleviates Liver Ischemia/Reperfusion Injury by Suppressing Autophagy and Apoptosis via the PPARα/PGC1α Signaling Pathway.Journal of clinical and translational hepatology · 2023Article
- Nuclear Receptor PPARα as a Therapeutic Target in Diseases Associated with Lipid Metabolism Disorders.Nutrients · 2023Review
- Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study.Environment international · 2023Article
- Air-ventilated normothermic machine perfusion alleviates hepatic injury from DCD rat through CYP1A2.Heliyon · 2023Article
- Hydrogen alleviated cognitive impairment and blood‒brain barrier damage in sepsis-associated encephalopathy by regulating ABC efflux transporters in a PPARα-dependent manner.BMC neuroscience · 2023Article
- Bioinformatic analyses reveal the prognostic significance and potential role of ankyrin 3 (ANK3) in kidney renal clear cell carcinoma.Genomics & informatics · 2023Article
- Bioinformatic analysis highlights SNHG6 as a putative prognostic biomarker for kidney renal papillary cell carcinoma.BMC urology · 2023Article
- Review
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7 authors at 5 institutions in 1 country.
Funding
Abstract
Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-α (PPARα) as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as a siRNA specific to PPARα, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.