ArticleMolecular cancer therapeutics2010
Schweinfurthin A selectively inhibits proliferation and Rho signaling in glioma and neurofibromatosis type 1 tumor cells in a NF1-GRD-dependent manner.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Glioblastoma in pregnant patient with pathologic and exogenous sex hormone exposure and family history of high-grade glioma: A case report and review of the literature.Surgical neurology international · 2023Article
- Therapeutic Potential of 5'-Methylschweinfurthin G in Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma.Viruses · 2022Article
- Molecular and cellular dissection of the oxysterol-binding protein cycle through a fluorescent inhibitor.The Journal of biological chemistry · 2020Article
- Chemical Diversity and Biological Activity of African Propolis.Progress in the chemistry of organic natural products · 2019Article
- Schweinfurthins A-Q: isolation, synthesis, and biochemical properties.RSC advances · 2018Review
- Anticancer activity of taraxerol acetate in human glioblastoma cells and a mouse xenograft model via induction of autophagy and apoptotic cell death, cell cycle arrest and inhibition of cell migration.Molecular medicine reports · 2016Article
- Article
- RNA interference‑mediated knockdown of translationally controlled tumor protein induces apoptosis, and inhibits growth and invasion in glioma cells.Molecular medicine reports · 2015Article
- Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Small molecule schweinfurthins selectively inhibit cancer cell proliferation and mTOR/AKT signaling by interfering with trans-Golgi-network trafficking.Cancer biology & therapy · 2015Article
- Calcium and P-glycoprotein independent synergism between schweinfurthins and verapamil.Cancer biology & therapy · 2015Article
- Quantitative analysis of F-actin redistribution in astrocytoma cells treated with candidate pharmaceuticals.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2014Article
- Regulation of cholesterol biosynthesis and cancer signaling.Current opinion in pharmacology · 2012Review
- Functional evaluation of a fluorescent schweinfurthin: mechanism of cytotoxicity and intracellular quantification.Molecular pharmacology · 2012Article
- Nf1 RasGAP inhibition of LIMK2 mediates a new cross-talk between Ras and Rho pathways.PloS one · 2012Article
- Relevance of the C-5 position to schweinfurthin induced cytotoxicity.Bioorganic & medicinal chemistry · 2011Article
- Article
- Discovery of a small molecule targeting IRA2 deletion in budding yeast and neurofibromin loss in malignant peripheral nerve sheath tumor cells.Molecular cancer therapeutics · 2011Article
- Natural products reveal cancer cell dependence on oxysterol-binding proteins.Nature chemical biology · 2011Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Neurofibromatosis type 1 (NF1) is the most common genetic disease affecting the nervous system. Patients typically develop many tumors over their lifetime, leading to increased morbidity and mortality. The NF1 gene, mutated in NF1, is also commonly mutated in sporadic glioblastoma multiforme (GBM). Because both NF1 and GBM are currently incurable, new therapeutic approaches are clearly needed. Natural products represent an opportunity to develop new therapies, as they have been evolutionarily selected to play targeted roles in organisms. Schweinfurthin A is a prenylated stilbene natural product that has previously shown specific inhibitory activity against brain and hematopoietic tumor lines. We show that patient-derived GBM and NF1 malignant peripheral nerve sheath tumor (MPNST) lines, as well as tumor lines derived from the Nf1-/+;Trp53-/+ (NPcis) mouse model of astrocytoma and MPNST are highly sensitive to inhibition by schweinfurthin A and its synthetic analogs. In contrast, primary mouse astrocytes are resistant to the growth inhibitory effects of schweinfurthin A, suggesting that schweinfurthin A may act specifically on tumor cells. Stable transfection of the GTPase-activating protein related domain of Nf1 into Nf1-/-;Trp53-/- astrocytoma cells confers resistance to schweinfurthin A. In addition, the profound effect of schweinfurthin A on dynamic reorganization of the actin cytoskeleton led us to discover that schweinfurthin A inhibits growth factor-stimulated Rho signaling. In summary, we have identified a class of small molecules that specifically inhibit growth of cells from both central and peripheral nervous system tumors and seem to act on NF1-deficient cells through cytoskeletal reorganization correlating to changes in Rho signaling.
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Registered trials
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