ArticleProceedings of the National Academy of Sciences of the United States of America2004
Simvastatin induces apoptosis of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and delays development of EBV lymphomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 85 citations in OpenAlex.
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- Review
- A CRISPR-Cas9 screen Reveals STEEP1 as a Key Host Dependency Factor for Epstein-Barr Virus Latent Membrane Protein 1 Trafficking and Signaling.bioRxiv : the preprint server for biology · 2026Article
- LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism.Cell death discovery · 2024Article
- Statins abrogate gemcitabine-induced PD-L1 expression in pancreatic cancer-associated fibroblasts and cancer cells with improved therapeutic outcome.Cancer immunology, immunotherapy : CII · 2023Article
- Cholesterol metabolism and lipid droplet vacuoles; a potential target for the therapy of aggressive lymphoma.Journal of clinical and experimental hematopathology : JCEH · 2022Article
- Lipid homeostasis and mevalonate pathway in COVID-19: Basic concepts and potential therapeutic targets.Progress in lipid research · 2021Review
- Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.Frontiers in pharmacology · 2021Review
- Epstein-Barr virus subverts mevalonate and fatty acid pathways to promote infected B-cell proliferation and survival.PLoS pathogens · 2019Article
- Updates to Binding MOAD (Mother of All Databases): Polypharmacology Tools and Their Utility in Drug Repurposing.Journal of molecular biology · 2019Article
- Curbing Lipids: Impacts ON Cancer and Viral Infection.International journal of molecular sciences · 2019Review
- Small-Molecule Modulation of Lipid-Dependent Cellular Processes against Cancer: Fats on the Gunpoint.BioMed research international · 2018Review
- Viral MicroRNAs Repress the Cholesterol Pathway, and 25-Hydroxycholesterol Inhibits Infection.mBio · 2017Article
- Type I Interferon Counteracts Antiviral Effects of Statins in the Context of Gammaherpesvirus Infection.Journal of virology · 2016Article
- A Viral microRNA Cluster Regulates the Expression of PTEN, p27 and of a bcl-2 Homolog.PLoS pathogens · 2016Article
- An AIDS-defining neoplasm in a 30-year-old man on highly active antiretroviral therapy: a forgotten diagnosis?BMJ case reports · 2014Article
- Article
- Ascorbic acid kills Epstein-Barr virus positive Burkitt lymphoma cells and Epstein-Barr virus transformed B-cells in vitro, but not in vivo.Leukemia & lymphoma · 2013Article
- Epstein-Barr virus LMP1 modulates lipid raft microdomains and the vimentin cytoskeleton for signal transduction and transformation.Journal of virology · 2013Article
- Simvastatin enhances protection against Listeria monocytogenes infection in mice by counteracting Listeria-induced phagosomal escape.PloS one · 2013Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Simvastatin and pravastatin are inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, and are used as antihypercholesterolemia drugs. Simvastatin, but not pravastatin, binds to the inserted domain of leukocyte function antigen (LFA)-1 and inhibits the function of LFA-1, including adhesion and costimulation of lymphocytes. Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) express high levels of LFA-1 on their surface and grow in tight clumps. Here we show that simvastatin (2 microM) inhibits clump formation and induces apoptosis of EBV-transformed LCLs. The apoptosis-inducing effect of simvastatin depends on binding to the inserted domain of LFA-1. Simvastatin, but not pravastatin, dissociates EBV latent membrane protein 1 from lipid rafts of LCLs, resulting in down-regulation of nuclear factor kappaB activity and induction of apoptosis. Analysis of multiple EBV-positive and -negative cell lines indicated that both LFA-1 and EBV latent membrane protein 1 expression were required for simvastatin's effects. Administration of simvastatin to severe combined immunodeficiency mice followed by inoculation with LCLs resulted in delayed development of EBV lymphomas and prolonged survival of animals. To our knowledge, this is the first report in which a drug that targets LFA-1 has been used to treat B cell lymphoma. These data suggest that simvastatin may have promise for treatment or prevention of EBV-associated lymphomas that occur in immunocompromised persons.
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