ArticleMolecular and cellular biology2015
Molecular mechanisms of fenofibrate-induced metabolic catastrophe and glioblastoma cell death.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
- Structure-guided optimisation of fenofibrate-derived oxidative phosphorylation inhibitors to modify tumour hypoxia.RSC medicinal chemistry · 2026Article
- Cannabigerol and Cannabichromene Induce Lung Cancer Cell Death and Apoptosis-Contribution of PPARα to Cannabigerol Effects.Antioxidants (Basel, Switzerland) · 2026Article
- Fenofibrate as an anti-cancer treatment: an in vitro study on glioblastoma cells at various oxygen levels and on normal astrocytes.Cancer cell international · 2026Article
- The Anti-proliferative Effects of Anandamide and Oleamide in Glioblastoma Cell Lines Recruit Mitochondrial and PPAR-γ Receptor Modulation.Neurochemical research · 2026Article
- Endothelial activation during the diapedesis of cancer cells: between the kiss of death and therapeutic breakthrough.Cellular & molecular biology letters · 2025Review
- Bypassing Blood-Brain Barrier and Glucose Dependency of Anti-Glioblastoma Drug Candidates Targeting Mitochondrial Respiration.Journal of cellular physiology · 2025Article
- Cardiolipin Dysregulation in Glioblastoma-Effects on Mitochondrial Function Tumor Cell Death and Sensitivity to Mitochondria-Targeting Drugs.Journal of cellular physiology · 2025Review
- Oxidative phosphorylation related gene COA6 is a novel indicator for the prognosis and immune response in lung adenocarcinoma.Scientific reports · 2024Article
- Article
- Identification of a Difluorinated Alkoxy Sulfonyl Chloride as a Novel Antitumor Agent for Hepatocellular Carcinoma through Activating Fumarate Hydratase Activity.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Melatonin and Its Metabolites Can Serve as Agonists on the Aryl Hydrocarbon Receptor and Peroxisome Proliferator-Activated Receptor Gamma.International journal of molecular sciences · 2023Article
- Computational modeling and synthesis of pyridine variants of benzoyl-phenoxy-acetamide with high glioblastoma cytotoxicity and brain tumor penetration.Scientific reports · 2023Article
- In Situ Vaccination with Mitochondria-Targeting Immunogenic Death Inducer Elicits CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Mitochondria Deregulations in Cancer Offer Several Potential Targets of Therapeutic Interventions.International journal of molecular sciences · 2023Review
- Computational modeling and synthesis of Pyridine variants of Benzoyl-Phenoxy-Acetamide with high glioblastoma cytotoxicity and brain tumor penetration.Research square · 2023Article
- Methylmalonic Acid Impairs Cell Respiration and Glutamate Uptake in C6 Rat Glioma Cells: Implications for Methylmalonic Acidemia.Cellular and molecular neurobiology · 2023Article
- Acquired drug resistance interferes with the susceptibility of prostate cancer cells to metabolic stress.Cellular & molecular biology letters · 2022Article
- Article
- Long-Term Fenofibrate Treatment Stimulates the Phenotypic Microevolution of Prostate Cancer Cells In Vitro.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Fenofibrate (FF) is a common lipid-lowering drug and a potent agonist of the peroxisome proliferator-activated receptor alpha (PPARα). FF and several other agonists of PPARα have interesting anticancer properties, and our recent studies demonstrate that FF is very effective against tumor cells of neuroectodermal origin. In spite of these promising anticancer effects, the molecular mechanism(s) of FF-induced tumor cell toxicity remains to be elucidated. Here we report a novel PPARα-independent mechanism explaining FF's cytotoxicity in vitro and in an intracranial mouse model of glioblastoma. The mechanism involves accumulation of FF in the mitochondrial fraction, followed by immediate impairment of mitochondrial respiration at the level of complex I of the electron transport chain. This mitochondrial action sensitizes tested glioblastoma cells to the PPARα-dependent metabolic switch from glycolysis to fatty acid β-oxidation. As a consequence, prolonged exposure to FF depletes intracellular ATP, activates the AMP-activated protein kinase-mammalian target of rapamycin-autophagy pathway, and results in extensive tumor cell death. Interestingly, autophagy activators attenuate and autophagy inhibitors enhance FF-induced glioblastoma cytotoxicity. Our results explain the molecular basis of FF-induced glioblastoma cytotoxicity and reveal a new supplemental therapeutic approach in which intracranial infusion of FF could selectively trigger metabolic catastrophe in glioblastoma cells.
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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.