ArticleeLife2016
The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- From Phytotoxin to Cell-Death Probe: Ophiobolin A and Related Sesterterpenoids in Membrane Stress and Non-Apoptotic Cell Death.Molecules (Basel, Switzerland) · 2026Review
- Derivatization of ophiobolin A and cytotoxicity toward breast and glioblastoma cancer stem cells: Varying the ketone and unsaturated aldehyde moieties.Bioorganic & medicinal chemistry letters · 2025Article
- Ophiobolin A derivatives with enhanced activities under tumor-relevant acidic conditions.Bioorganic & medicinal chemistry letters · 2024Article
- Molecular Characterization and Expression Analysis of a Gene Encoding 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGR) fromJournal of fungi (Basel, Switzerland) · 2024Article
- A chronic stress-induced microbiome perturbation, highly enriched inInternational journal of medical sciences · 2024Article
- Anti-Proliferative and Apoptotic Activities ofLife (Basel, Switzerland) · 2023Article
- Therapeutic vulnerabilities of cancer stem cells and effects of natural products.Natural product reports · 2023Review
- Evolving Diagnostic and Treatment Strategies for Pediatric CNS Tumors: The Impact of Lipid Metabolism.Biomedicines · 2023Review
- Lipidomic profiling in the Strong Heart Study identified American Indians at risk of chronic kidney disease.Kidney international · 2022Article
- A Stereoselective Photoinduced Cycloisomerization Inspired by Ophiobolin A.Organic letters · 2022Article
- A Modeling and Analysis Study Reveals That CaMKII in Synaptic Plasticity Is a Dominant Affecter in CaM Systems in a T286 Phosphorylation-Dependent Manner.Molecules (Basel, Switzerland) · 2022Article
- Bilayer Forming Phospholipids as Targets for Cancer Therapy.International journal of molecular sciences · 2022Review
- SMAC/Diablo controls proliferation of cancer cells by regulating phosphatidylethanolamine synthesis.Molecular oncology · 2021Article
- The phospholipid membrane compositions of bacterial cells, cancer cell lines and biological samples from cancer patients.Chemical science · 2021Review
- Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets.International journal of molecular sciences · 2021Article
- Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A.Scientific reports · 2021Article
- Structural insights into phosphatidylethanolamine formation in bacterial membrane biogenesis.Scientific reports · 2021Article
- Mathermycin, an anti-cancer molecule that targets cell surface phospholipids.Toxicology and applied pharmacology · 2021Article
- Article
- A Covalent Calmodulin Inhibitor as a Tool to Study Cellular Mechanisms of K-Ras-Driven Stemness.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Phenotypic screens allow the identification of small molecules with promising anticancer activity, but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads. Here, we used a loss-of-function genetic screen in human haploid KBM7 cells to discover the mechanism of action of the anticancer natural product ophiobolin A (OPA). We found that genetic inactivation of de novo synthesis of phosphatidylethanolamine (PE) mitigates OPA cytotoxicity by reducing cellular PE levels. OPA reacts with the ethanolamine head group of PE in human cells to form pyrrole-containing covalent cytotoxic adducts and these adducts lead to lipid bilayer destabilization. Our characterization of this unusual cytotoxicity mechanism, made possible by unbiased genetic screening in human cells, suggests that the selective antitumor activity displayed by OPA may be due to altered membrane PE levels in cancer cells.
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What OpenQuestion holds
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.