ArticleNeuro-oncology2016
Components of the eIF4F complex are potential therapeutic targets for malignant peripheral nerve sheath tumors and vestibular schwannomas.
Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Activity of Didesmethylrocaglamide in High Grade Serous Ovarian Cancer Using Preclinical In Vitro and In Vivo Models.Journal of natural products · 2026Article
- Matrix Metalloproteinase‑9 (MMP-9) Activatable Gold Nanoparticles forACS applied nano materials · 2026Article
- Anti-tumor effects of the eIF4A inhibitor didesmethylrocaglamide and its derivatives in human and canine osteosarcomas.Scientific reports · 2024Article
- Anti-tumor Effects of the eIF4A Inhibitor Didesmethylrocaglamide and Its Derivatives in Human and Canine Osteosarcomas.Research square · 2024Article
- eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation.Nucleic acids research · 2023Article
- Eukaryotic translation initiation factor 4A1 in the pathogenesis and treatment of cancers.Frontiers in molecular biosciences · 2023Review
- Copy number variation of EIF4A2 loci related to phenotypic traits in Chinese cattle.Veterinary medicine and science · 2022Article
- Discovery of Anticancer Agents of Diverse Natural Origin.Journal of natural products · 2022Article
- Proteomics reveal cap-dependent translation inhibitors remodel the translation machinery and translatome.Cell reports · 2021Article
- Update on Phytochemical and Biological Studies on Rocaglate Derivatives from Aglaia Species.Planta medica · 2021Review
- Article
- Expression and Functional Roles of Eukaryotic Initiation Factor 4A Family Proteins in Human Cancers.Frontiers in cell and developmental biology · 2021Review
- Neurofibromatosis: Molecular Pathogenesis and Natural Compounds as Potential Treatments.Frontiers in oncology · 2021Review
- High expression of eIF4A2 is associated with a poor prognosis in esophageal squamous cell carcinoma.Oncology letters · 2020Article
- Targeting Protein Translation by Rocaglamide and Didesmethylrocaglamide to Treat MPNST and Other Sarcomas.Molecular cancer therapeutics · 2020Article
- Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.Leukemia · 2020Article
- MicroRNA-5195-3p enhances the chemosensitivity of triple-negative breast cancer to paclitaxel by downregulating EIF4A2.Cellular & molecular biology letters · 2019Article
- Emerging therapeutic targets for neurofibromatosis type 1.Expert opinion on therapeutic targets · 2018Review
- Overexpression of eIF4F components in meningiomas and suppression of meningioma cell growth by inhibiting translation initiation.Experimental neurology · 2018Article
- Discovery of Anticancer Agents of Diverse Natural Origin.Anticancer research · 2016Review
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12 authors.
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Abstract
backgroundThe eukaryotic initiation factor 4F (eIF4F) complex plays a pivotal role in protein translation initiation; however, its importance in malignant and benign Schwann cell tumors has not been explored, and whether blocking eIF4F function is effective for treating these tumors is not known.
methodsImmunostaining was performed on human malignant peripheral nerve sheath tumors (MPNSTs) and vestibular schwannomas (VSs) for eIF4F components. The role of eIF4A and eIF4E in cell growth was assessed by RNA interference. Various natural compounds were screened for their growth-inhibitory activity. Flow cytometry and Western blotting were performed to characterize the action of silvestrol, and its antitumor activity was verified in orthotopic mouse models.
resultsMPNSTs and VSs frequently overexpressed eIF4A, eIF4E, and/or eIF4G. Depletion of eIF4A1, eIF4A2, and eIF4E substantially reduced MPNST cell growth. From screening a panel of plant-derived compounds, the eIF4A inhibitor silvestrol was identified as a leading agent with nanomolar IC50 values in MPNST and VS cells. Silvestrol induced G2/M arrest in both NF1-deficient and NF1-expressing MPNST cells and primary VS cells. Silvestrol consistently decreased the levels of multiple cyclins, Aurora A, and mitogenic kinases AKT and ERKs. Silvestrol treatment dramatically suppressed tumor growth in mouse models for NF1(-/-) MPNST and Nf2(-/-) schwannoma. This decreased tumor growth was accompanied by elevated phospho-histone H3 and TUNEL labeling, consistent with G2/M arrest and apoptosis in silvestrol-treated tumor cells.
conclusionsThe eIF4F complex is a potential therapeutic target in MPNSTs and VS, and silvestrol may be a promising agent for treating these tumors.
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