ArticlePloS one2013
Therapeutic potential of the translation inhibitor silvestrol in hepatocellular cancer.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 66 citations in OpenAlex.
- Rocaglates and pateamines target the DEAD-box RNA helicase eIF4A from Schistosoma mansoni and demonstrate anti-schistosomal activity in vitro.Scientific reports · 2026Article
- The continuing need for taxonomic input in phytochemical research.Journal of ethnopharmacology · 2026Review
- Silvestrol inhibits nasopharyngeal carcinoma cells and synergizes with CX-5461: Insights from a proteomics study.Molecular and clinical oncology · 2025Article
- Unlocking the biological potential of methyl antcinate A: a new frontier in cancer and inflammation application.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Inhibition of Ribosome Biogenesis In Vivo Causes p53-Dependent Death and p53-Independent Dysfunction.Cellular and molecular gastroenterology and hepatology · 2025Article
- Protein-RNA interactions mediated by silvestrol-insight into a unique molecular clamp.Nucleic acids research · 2024Article
- The role of eIF4F-driven mRNA translation in regulating the tumour microenvironment.Nature reviews. Cancer · 2023Review
- Comparing the Effects of Rocaglates on Energy Metabolism and Immune Modulation on Cells of the Human Immune System.International journal of molecular sciences · 2023Article
- Translational Control of Metabolism and Cell Cycle Progression in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- The dark side of mRNA translation and the translation machinery in glioblastoma.Frontiers in cell and developmental biology · 2023Review
- In Vitro Safety, Off-Target and Bioavailability Profile of the Antiviral Compound Silvestrol.Pharmaceuticals (Basel, Switzerland) · 2022Article
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- Collective Learnings of Studies of Stress Granule Assembly and Composition.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Comparative phytochemistry of flavaglines (= rocaglamides), a group of highly bioactive flavolignans fromPhytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2022Review
- Proteomics reveal cap-dependent translation inhibitors remodel the translation machinery and translatome.Cell reports · 2021Article
- Fasnall Induces Atypically Transient Stress Granules Independently of FASN Inhibition.iScience · 2020Article
- The eIF4A inhibitor silvestrol sensitizes T-47D ductal breast carcinoma cells to external-beam radiotherapy.Clinical and translational radiation oncology · 2020Article
- Natural antiviral compound silvestrol modulates human monocyte-derived macrophages and dendritic cells.Journal of cellular and molecular medicine · 2020Article
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Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsAlthough hepatocellular cancers (HCC) frequently arise in the setting of fibrosis and a hepatic regenerative response requiring new cell growth, therapeutic strategies for these cancers have not targeted protein synthesis. Silvestrol, a rocaglate isolated from Aglaiafoveolata, can inhibit protein synthesis by modulating the initiation of translation through the eukaryotic initiation factor 4A. In this study, we evaluated the therapeutic efficacy of silvestrol for HCC.
methodsThe efficacy of silvestrol was examined using human HCC cells in vitro using an orthotopic tumor cell xenograft model in a fibrotic liver. The impact of silvestrol on the liver was assessed in vivo in wild-type mice.
resultsSilvestrol inhibited cell growth with an IC50 of 12.5-86 nM in four different HCC cell lines. In vitro, silvestrol increased apoptosis and caspase 3/7 activity accompanied by loss of mitochondrial membrane potential and decreased expression of Mcl-1 and Bcl-xL. A synergistic effect was observed when silvestrol was combined with other therapeutic agents, with a dose-reduction index of 3.42-fold with sorafenib and 1.75-fold with rapamycin at a fractional effect of 0.5. In vivo, an antitumor effect was observed with 0.4 mg/kg silvestrol compared to controls after one week, and survival of tumor-bearing mice was improved with a median survival time of 42 and 28 days in the silvestrol and control groups, respectively. The effect on survival was not observed in orthotopic xenografts in non-fibrotic livers. Silvestrol treatment in vivo did not alter liver structure.
conclusionsThese data identify silvestrol as a novel, structurally unique drug with potent anticancer activity for HCC and support the potential value of targeting initiation of translation in the treatment of HCC.
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