ArticleBlood2009
The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
What it found
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The trial behind it
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Who cites it
97 citing papers in PubMed, 166 citations in OpenAlex.
- Trial
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- 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
- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- Potent anti-coronaviral activity of pateamines and new insights into their mode of action.Heliyon · 2024Article
- Medicinal chemistry approaches to target the MNK-eIF4E axis in cancer.RSC medicinal chemistry · 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
- Article
- EIF4A inhibition targets bioenergetic homeostasis in AML MOLM-14 cells in vitro and in vivo and synergizes with cytarabine and venetoclax.Journal of experimental & clinical cancer research : CR · 2022Article
- In Vitro Safety, Off-Target and Bioavailability Profile of the Antiviral Compound Silvestrol.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Pharmacological modulation of Kv1.3 potassium channel selectively triggers pathological B lymphocyte apoptosis in vivo in a genetic CLL model.Journal of experimental & clinical cancer research : CR · 2022Article
- Comparative phytochemistry of flavaglines (= rocaglamides), a group of highly bioactive flavolignans fromPhytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2022Review
- Targeting Mcl-1 by AMG-176 During Ibrutinib and Venetoclax Therapy in Chronic Lymphocytic Leukemia.Frontiers in oncology · 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
- A forward genetic screen identifies modifiers of rocaglate responsiveness.Scientific reports · 2021Article
- Targeted inhibition of eIF4A suppresses B-cell receptor-induced translation and expression of MYC and MCL1 in chronic lymphocytic leukemia cells.Cellular and molecular life sciences : CMLS · 2021Article
- Strategies targeting FLT3 beyond the kinase inhibitors.Pharmacology & therapeutics · 2021Review
- Cytotoxic and Apoptotic Activity of Aglaforbesin Derivative Isolated from Aglaia loheri Merr. on HCT116 Human Colorectal Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2021Article
37 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
20 authors at 2 institutions in 1 country.
Funding
Abstract
Therapeutic options for advanced B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are limited. Available treatments can also deplete T lymphocytes, leaving patients at risk of life-threatening infections. In the National Cancer Institute cell line screen, the structurally unique natural product silvestrol produces an unusual pattern of cytotoxicity that suggests activity in leukemia and selectivity for B cells. We investigated silvestrol efficacy using primary human B-leukemia cells, established B-leukemia cell lines, and animal models. In CLL cells, silvestrol LC(50) (concentration lethal to 50%) is 6.9 nM at 72 hours. At this concentration, there is no difference in sensitivity of cells from patients with or without the del(17p13.1) abnormality. In isolated cells and whole blood, silvestrol is more cytotoxic toward B cells than T cells. Silvestrol causes early reduction in Mcl-1 expression due to translational inhibition with subsequent mitochondrial damage, as evidenced by reactive oxygen species generation and membrane depolarization. In vivo, silvestrol causes significant B-cell reduction in Emu-Tcl-1 transgenic mice and significantly extends survival of 697 xenograft severe combined immunodeficient (SCID) mice without discernible toxicity. These data indicate silvestrol has efficacy against B cells in vitro and in vivo and identify translational inhibition as a potential therapeutic target in B-cell leukemias.
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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.