ArticleJournal of hematology & oncology2013
Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia.
Article in Journal of hematology & oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
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- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- MicroRNAs Associated with a Bad Prognosis in Acute Myeloid Leukemia and Their Impact on Macrophage Polarization.Biomedicines · 2024Review
- Phytochemicals and bioactive compounds effective against acute myeloid leukemia: A systematic review.Food science & nutrition · 2023Article
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- The dark side of mRNA translation and the translation machinery in glioblastoma.Frontiers in cell and developmental biology · 2023Review
- Natural Products as Anticancer Agents: Current Status and Future Perspectives.Molecules (Basel, Switzerland) · 2022Review
- CD44v6 chimeric antigen receptor T cell specificity towards AML with FLT3 or DNMT3A mutations.Clinical and translational medicine · 2022Article
- Resveratrol triggers anti-proliferative and apoptotic effects in FLT3-ITD-positive acute myeloid leukemia cells via inhibiting ceramide catabolism enzymes.Medical oncology (Northwood, London, England) · 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
- Update on Phytochemical and Biological Studies on Rocaglate Derivatives from Aglaia Species.Planta medica · 2021Review
- Strategies targeting FLT3 beyond the kinase inhibitors.Pharmacology & therapeutics · 2021Review
- OTS167 blocks FLT3 translation and synergizes with FLT3 inhibitors in FLT3 mutant acute myeloid leukemia.Blood cancer journal · 2021Article
- Beyond regulations at DNA levels: A review of epigenetic therapeutics targeting cancer stem cells.Cell proliferation · 2021Review
- Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Clinical Applications of MicroRNAs in Acute Myeloid Leukemia: A Mini-Review.Frontiers in oncology · 2021Review
- Promising Terpenes as Natural Antagonists of Cancer: An In-Silico Approach.Molecules (Basel, Switzerland) · 2019Article
- Cancer the'RBP'eutics-RNA-binding proteins as therapeutic targets for cancer.Pharmacology & therapeutics · 2019Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundActivating mutations [internal tandem duplication (ITD)] or overexpression of the FMS-like tyrosine kinase receptor-3 (FLT3) gene are associated with poor outcome in acute myeloid leukemia (AML) patients, underscoring the need for novel therapeutic approaches. The natural product silvestrol has potent antitumor activity in several malignancies, but its therapeutic impact on distinct molecular high-risk AML subsets remains to be fully investigated. We examined here the preclinical activity of silvestrol in FLT3-ITD and FLT3 wild-type (wt) AML.
methodsSilvestrol in vitro anti-leukemic activity was examined by colorimetric cell viability assay, colony-forming and flow cytometry assays assessing growth inhibition and apoptosis, respectively. Pharmacological activity of silvestrol on FLT3 mRNA translation, mRNA and protein expression was determined by RNA-immunoprecipitation, qRT-PCR and immunoblot analyses, respectively. Silvestrol in vivo efficacy was investigated using MV4-11 leukemia-engrafted mice.
resultsSilvestrol shows antileukemia activity at nanomolar concentrations both in FLT3-wt overexpressing (THP-1) and FLT3-ITD (MV4-11) expressing AML cell lines (IC50 = 3.8 and 2.7 nM, respectively) and patients' primary blasts [IC50 = ~12 nM (FLT3-wt) and ~5 nM (FLT3-ITD)]. Silvestrol increased apoptosis (~4fold, P = 0.0001), and inhibited colony-formation (100%, P < 0.0001) in primary blasts. Silvestrol efficiently inhibited FLT3 translation reducing FLT3 protein expression by 80-90% and decreased miR-155 levels (~60%), a frequently co-regulated onco-miR in FLT3-ITD-positive AML. The median survival of silvestrol-treated vs vehicle-treated mice was 63 vs 29 days post-engraftment, respectively (P < 0.0001).
conclusionsSilvestrol exhibits significant in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of FLT3 and miR-155 expression. These encouraging results warrant a rapid translation of silvestrol for clinical testing in AML.
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