ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Dual targeting of the cyclin/Rb/E2F and mitochondrial pathways in mantle cell lymphoma with the translation inhibitor silvestrol.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Silvestrol inhibits nasopharyngeal carcinoma cells and synergizes with CX-5461: Insights from a proteomics study.Molecular and clinical oncology · 2025Article
- eIF4A controls translation of estrogen receptor alpha and is a therapeutic target in advanced breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes.International journal of molecular sciences · 2023Article
- Genetic characterization and drug sensitivity study of newly derived HGBL double/triple-hit lymphoma cell lines.Blood advances · 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
- A forward genetic screen identifies modifiers of rocaglate responsiveness.Scientific reports · 2021Article
- The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo.Antiviral research · 2018Article
- FGFR1-Activated Translation of WNT Pathway Components with Structured 5' UTRs Is Vulnerable to Inhibition of EIF4A-Dependent Translation Initiation.Cancer research · 2018Article
- Discovery of Anticancer Agents of Diverse Natural Origin.Anticancer research · 2016Review
- Components of the eIF4F complex are potential therapeutic targets for malignant peripheral nerve sheath tumors and vestibular schwannomas.Neuro-oncology · 2016Article
- Mantle cell lymphoma in the era of precision medicine-diagnosis, biomarkers and therapeutic agents.Oncotarget · 2016Review
- Cyclopenta[b]benzofuran and Secodammarane Derivatives from the Stems of Aglaia stellatopilosa.Journal of natural products · 2016Article
- Article
- Emerging links between E2F control and mitochondrial function.Cancer research · 2015Review
- Article
- Rocaglamide, silvestrol and structurally related bioactive compounds from Aglaia species.Natural product reports · 2014Review
- Article
- Evidence for a functionally relevant rocaglamide binding site on the eIF4A-RNA complex.ACS chemical biology · 2013Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
purposeDuring cell-cycle progression, D-cyclins activate cyclin-dependent kinases (CDKs) 4/6 to inactivate Rb, permitting E2F1-mediated S-phase gene transcription. This critical pathway is typically deregulated in cancer, and novel inhibitory strategies would be effective in a variety of tumors. The protein synthesis inhibitor silvestrol has potent activity in B-cell leukemias via the mitochondrial pathway of apoptosis, and also reduces cyclin D1 expression in breast cancer and lymphoma cell lines. We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression. EXPERIMENTAL
designMantle cell lymphoma (MCL), characterized by elevated cyclin D1, was used as a model to test this approach. The cyclin D/Rb/E2F1 pathway was investigated in vitro using MCL cell lines and primary tumor cells. Silvestrol was also evaluated in vivo using an aggressive model of MCL.
resultsSilvestrol showed low nanomolar potency both in MCL cell lines and primary MCL tumor cells. D-cyclins were depleted with just 10 nmol/L silvestrol at 16 hours, with subsequent reductions of phosphorylated Rb, E2F1 protein, and E2F1 target transcription. As showed in other leukemias, silvestrol caused Mcl-1 depletion followed by mitochondrial depolarization and caspase-dependent apoptosis, effects not related to inhibition of CDK4/6. Silvestrol significantly (P < 0.0001) prolonged survival in a MCL xenograft model without detectable toxicity.
conclusionsThese data indicate that silvestrol effectively targets the cyclin/CDK/Rb pathway, and additionally induces cytotoxicity via intrinsic apoptosis. This dual activity may be an effective therapeutic strategy in MCL and other malignancies.
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