ArticleCell death & disease2013
HMG-CoA reductase inhibitors induce apoptosis of lymphoma cells by promoting ROS generation and regulating Akt, Erk and p38 signals via suppression of mevalonate pathway.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 147 citations in OpenAlex.
- Associations of different types of statins with the risk of open-angle glaucoma: a systematic review and network meta-analysis.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025Pooled it
- Association between statin use & risk of diffuse large B-cell lymphoma: A systematic review & meta-analysis.The Indian journal of medical research · 2023Pooled it
- Trial
- Are statins interferon's best friends? Mechanistic insights.Blood advances · 2026Article
- Pharmacological targeting of ferroptosis in cancer: mechanisms, tumor immunity, and translational challenges.Pharmacological reports : PR · 2026Review
- Protective Effects of Policosanol and Atorvastatin Co-Supplementation Against High-Cholesterol and High-Galactose Diet-Induced Metabolic and Organ Dysfunction in Zebrafish.International journal of molecular sciences · 2026Article
- Ultrasound-responsive nanodroplets activate the Hippo pathway via ROS-MST1-YAP cascade for breast cancer therapy.Ultrasonics sonochemistry · 2026Article
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
- Dose-dependent effects of atorvastatin on inflammatory response in endothelial cells: MMP/TIMP balance and in vitro wound closure assay.BMC molecular and cell biology · 2026Article
- Combination of Policosanol (RaydelPharmaceuticals (Basel, Switzerland) · 2026Article
- Mevalonic acid exerts procoagulant effect by potentiating factor Xa.Natural products and bioprospecting · 2026Article
- The E2F1-HMGCR axis promotes ferroptosis resistance in immune refractory tumor cells.Nature communications · 2025Article
- Association Between Statin Use and Glaucoma Risk: A Population-Based Study.Investigative ophthalmology & visual science · 2025Article
- HMG-CoA reductase inhibition preserves testicular function after torsion/detorsion by modulating oxidative stress and AKT signaling.Scientific reports · 2025Article
- ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions.Molecular biomedicine · 2025Review
- Drug repurposing in oncology: a path beyond the bottleneck.Medical oncology (Northwood, London, England) · 2025Review
- Article
- Statins as potential adjuvant therapy in lung cancer: a narrative review.Journal of thoracic disease · 2025Review
- The Role of Cholesterol Metabolism and Its Regulation in Tumor Development.Cancer medicine · 2025Review
- Cellular senescence in the tumor with a bone niche microenvironment: friend or foe?Clinical and experimental medicine · 2025Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used cholesterol-lowering drugs. Convincing evidence indicates that statins stimulate apoptotic cell death in several types of proliferating tumor cells in a cholesterol-lowering-independent manner. The objective here was to elucidate the molecular mechanism by which statins induce lymphoma cells death. Statins (atorvastatin, fluvastatin and simvastatin) treatment enhanced the DNA fragmentation and the activation of proapoptotic members such as caspase-3, PARP and Bax, but suppressed the activation of anti-apoptotic molecule Bcl-2 in lymphoma cells including A20 and EL4 cells, which was accompanied by inhibition of cell survival. Both increase in levels of reactive oxygen species (ROS) and activation of p38 MAPK and decrease in mitochondrial membrane potential and activation of Akt and Erk pathways were observed in statin-treated lymphoma cells. Statin-induced cytotoxic effects, DNA fragmentation and changes of activation of caspase-3, Akt, Erk and p38 were blocked by antioxidant (N-acetylcysteine) and metabolic products of the HMG-CoA reductase reaction, such as mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). These results suggests that HMG-CoA reductase inhibitors induce lymphoma cells apoptosis by increasing intracellular ROS generation and p38 activation and suppressing activation of Akt and Erk pathways, through inhibition of metabolic products of the HMG-CoA reductase reaction including mevalonate, FPP and GGPP.
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Registered trials
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.