ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Targeting of eEF1A with Amaryllidaceae isocarbostyrils as a strategy to combat melanomas.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 58 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed.
- Single-cell sequencing-guided discovery of narciclasine as a dual VCAM-1/ICAM-1 inhibitor for atherosclerosis management.Genes & diseases · 2027Article
- From Daffodils to Drug Leads: Amaryllidaceae Alkaloids Target Protein Translation in Chronic Lymphocytic Leukemia to Induce Selective Apoptosis.ACS pharmacology & translational science · 2026Article
- Overcoming Docetaxel Resistance in Prostate Cancer by Targeting Cell Cycle Progression with Narciclasine-Based Compounds.ACS omega · 2026Article
- Narciclasine reduces proliferation and migration of neuroblastoma cells and decreases FAK/PI3K pathway activation.Medical oncology (Northwood, London, England) · 2026Article
- Integrative Network-Based Transcriptomic Analysis Identifies Niclosamide as a Candidate Repositioned Drug for Breast Cancer.Breast cancer (Dove Medical Press) · 2026Article
- Narciclasine triggers apoptosis in osteosarcoma cells via JNK-mediated extrinsic and intrinsic pathways.International journal of medical sciences · 2026Article
- Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.International journal of molecular sciences · 2025Review
- Narciclasine enhances cisplatin-induced apoptotic cell death by inducing unfolded protein response-mediated regulation of NOXA and MCL1.Cellular & molecular biology letters · 2025Article
- Narciclasine inhibits vaccinia virus infection by activating the RhoA signaling pathway.Biosafety and health · 2024Article
- Exploiting Translation Machinery for Cancer Therapy: Translation Factors as Promising Targets.International journal of molecular sciences · 2024Review
- A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes.Cell · 2024Article
- Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art.International journal of molecular sciences · 2023Review
- Biochemical Analyses of Bioactive Extracts from Plants Native to Lampedusa, Sicily Minor Island.Plants (Basel, Switzerland) · 2022Article
- Amaryllidaceae Alkaloids Decrease the Proliferation, Invasion, and Secretion of Clinically Relevant Cytokines by Cultured Human Colon Cancer Cells.Biomolecules · 2022Article
- Article
- Structures and Biological Activities of Alkaloids Produced by Mushrooms, a Fungal Subgroup.Biomolecules · 2022Review
- Article
- Narciclasine targets STAT3 via distinct mechanisms in tamoxifen-resistant breast cancer cells.Molecular therapy oncolytics · 2022Article
- Narciclasine inhibits phospholipase A2 and regulates phospholipid metabolism to ameliorate psoriasis-like dermatitis.Frontiers in immunology · 2022Article
- Sphaeropsidin A: A Pimarane Diterpene with Interesting Biological Activities and Promising Practical Applications.Chembiochem : a European journal of chemical biology · 2021Review
Corrections and comments
- Erratum issuedERRATUM.2015
Authors and funding
17 authors.
Funding
Abstract
Melanomas display poor response rates to adjuvant therapies because of their intrinsic resistance to proapoptotic stimuli. This study indicates that such resistance can be overcome, at least partly, through the targeting of eEF1A elongation factor with narciclasine, an Amaryllidaceae isocarbostyril controlling plant growth. Narciclasine displays IC(50) growth inhibitory values between 30-100 nM in melanoma cell lines, irrespective of their levels of resistance to proapoptotic stimuli. Normal noncancerous cell lines are much less affected. At nontoxic doses, narciclasine also significantly improves (P=0.004) the survival of mice bearing metastatic apoptosis-resistant melanoma xenografts in their brain. The eEF1A targeting with narciclasine (50 nM) leads to 1) marked actin cytoskeleton disorganization, resulting in cytokinesis impairment, and 2) protein synthesis impairment (elongation and initiation steps), whereas apoptosis is induced at higher doses only (≥200 nM). In addition to molecular docking validation and identification of potential binding sites, we biochemically confirmed that narciclasine directly binds to human recombinant and yeast-purified eEF1A in a nanomolar range, but not to actin or elongation factor 2, and that 5 nM narciclasine is sufficient to impair eEF1A-related actin bundling activity. eEF1A is thus a potential target to combat melanomas regardless of their apoptosis-sensitivity, and this finding reconciles the pleiotropic cytostatic of narciclasine. -
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