ArticleCell death & disease2023
Combination treatment with FAAH inhibitors/URB597 and ferroptosis inducers significantly decreases the growth and metastasis of renal cell carcinoma cells via the PI3K-AKT signaling pathway.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- Neurexophilin 4 facilitates the malignant progression of kidney renal clear cell carcinoma by regulating PI3K/AKT-mediated glycolysis.Molecular genetics and genomics : MGG · 2026Article
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- Zileuton protects pancreatic stellate cells from oxidative stress and ferroptosis by modulating the Nrf2 pathway and mitochondrial activity.Journal of physiology and biochemistry · 2026Article
- MT1G promotes the progression of ccRCC by suppressing ferroptosis through activation of the PI3K-AKT pathway.Translational oncology · 2026Article
- FAAH initiates a positive feedback loop to promote lung adenocarcinoma progression through inhibition of ferroptosis.Cell death and differentiation · 2026Article
- Ferroptosis as a therapeutic target in cancer: mechanisms, immune interactions, and emerging strategies.Molecular cancer · 2026Review
- Ferroptosis in renal cell carcinoma: integrative multi-omics insights and therapeutic perspectives.International journal of surgery (London, England) · 2026Article
- The role of ferroptosis in renal cell carcinoma: molecular mechanisms and therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Advancements in CDK-based Dual-target Inhibitors for Cancer Therapy.Current medicinal chemistry · 2026Review
- Exploring Natural Products to Target Ferroptosis in Urologic Malignancies: Advancements from Molecular Mechanisms to Therapeutic Strategies.Chinese journal of integrative medicine · 2025Review
- Ferroptosis, a Distinct Form of Cell Death, and Research Progress on Its Modulators.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Article
- Prognostic Significance ofBiology · 2025Article
- Pisces: A multi-modal data augmentation approach for drug combination synergy prediction.Cell genomics · 2025Article
- Integrated analysis of polytranscriptomics reveals TNFSF ligand genes in pancreatic cancer prognosis and immune regulation.BMC immunology · 2025Article
- Photodynamic therapeutic activity of novel porphyrins against lung squamous cell carcinoma.BMC cancer · 2025Article
- The Ferroptosis-Mitochondrial Axis in Depression: Unraveling the Feedforward Loop of Oxidative Stress, Metabolic Homeostasis Dysregulation, and Neuroinflammation.Antioxidants (Basel, Switzerland) · 2025Review
- Polygonum multiflorum Stilbene Glycoside Oligomers induce the ferroptosis of triple negative breast cancer cells.BMC cancer · 2025Article
- Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Mitigation of cisplatin-induced acute kidney injury through oral administration of fatty acid amide hydrolase inhibitor PF-04457845.The Journal of pharmacology and experimental therapeutics · 2025Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis, a nonapoptotic form of programmed cell death characterized by significant iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating the potential of combinational strategies for treating cancer in the future. In this study, we explored the combinational effects of lipid metabolism compounds and ferroptosis inducers on renal cell carcinoma (RCC) cells. We found potent synergy of the fatty acid amide hydrolase (FAAH) inhibitor URB597 with ferroptosis inducer (1S, 3R)-RSL3 (RSL3) in inhibiting the growth and metastasis of RCC cells both in vitro and in vivo via induction of G1 cell cycle arrest and promotion of the production of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and cytosolic reactive oxygen species (ROS). In addition, inhibition of FAAH increased the sensitivity of RCC cells to ferroptosis. Genome-wide RNA sequencing indicated that the combination of URB597 and RSL3 has more significant effects on regulation of the expression of genes related to cell proliferation, the cell cycle, cell migration and invasion, and ferroptosis than either single agent alone. Moreover, we found that combinational treatment modulated the sensitivity of RCC cells to ferroptosis via the phosphatidylinositol 3 kinase (PI3K)-AKT signaling pathway. These data demonstrate that dual targeting of FAAH and ferroptosis could be a promising strategy for treating RCC.
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