ArticleInvestigative ophthalmology & visual science2006
Small molecule anti-angiogenic probes of the ubiquitin proteasome pathway: potential application to choroidal neovascularization.
Article in Investigative ophthalmology & visual science, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 58 citations in OpenAlex.
- Ashwagandha (Withania Somnifera): a comprehensive narrative review of its role in enhancing physical performance and health.Nutrition & metabolism · 2026Review
- Withaferin A inhibits EBV-driven lymphomagenesis through multiple mechanisms, including EBNA1 degradation.Blood · 2026Article
- Review
- Review
- Galectin-1 and -3 in high amounts inhibit angiogenic properties of human retinal microvascular endothelial cells in vitro.PloS one · 2022Article
- Effects of Ashwagandha (Journal of functional morphology and kinesiology · 2021Review
- Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC.Frontiers in oncology · 2020Article
- Angiogenic and Immunologic Proteins Identified by Deep Proteomic Profiling of Human Retinal and Choroidal Vascular Endothelial Cells: Potential Targets for New Biologic Drugs.American journal of ophthalmology · 2018Article
- Synergistic inhibition of glioma cell proliferation by Withaferin A and tumor treating fields.Journal of neuro-oncology · 2017Article
- Recent Advances in the Development of Antineoplastic Agents Derived from Natural Products.Drugs · 2015Review
- Vimentin Phosphorylation Underlies Myofibroblast Sensitivity to Withaferin A In Vitro and during Corneal Fibrosis.PloS one · 2015Article
- Natural product inhibitors of ocular angiogenesis.Experimental eye research · 2014Review
- JNK-NQO1 axis drives TAp73-mediated tumor suppression upon oxidative and proteasomal stress.Cell death & disease · 2014Article
- Structure-activity relationship (SAR) of withanolides to inhibit Hsp90 for its activity in pancreatic cancer cells.Investigational new drugs · 2014Article
- In vitro inhibition of angiogenesis by antibodies directed against the 37kDa/67kDa laminin receptor.PloS one · 2013Article
- Withaferin A effectively targets soluble vimentin in the glaucoma filtration surgical model of fibrosis.PloS one · 2013Article
- Corneal antifibrotic switch identified in genetic and pharmacological deficiency of vimentin.The Journal of biological chemistry · 2012Article
- A robust model for simultaneously inducing corneal neovascularization and retinal gliosis in the mouse eye.Molecular vision · 2011Article
- Withaferin A targets intermediate filaments glial fibrillary acidic protein and vimentin in a model of retinal gliosis.The Journal of biological chemistry · 2010Article
- Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.Journal of inflammation (London, England) · 2009Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo characterize the angiogenic and inflammatory responses of human choroidal endothelial cells (HCECs) to stimulators and inhibitors of the ubiquitin proteasome pathway (UPP).
methodsThe regulation of the UPP by the inhibitor withaferin A and its congener, withanolide D, two natural products derived from the medicinal plant Withania somnifera was assessed in the three-dimensional endothelial cell sprouting assay (3D-ECSA), by using HCEC- and human umbilical vein endothelial cell (HUVEC)-derived spheroids embedded in a collagen I matrix. Western blot analysis was used to investigate the effect of withanolides on IkappaB-alpha, polyubiquitination, and heme oxygenase (HO)-1 regulation in HCEC and HUVEC cultures.
resultsHCECs, like HUVECs, responded to fibroblast growth factor-2, vascular endothelial growth factor, and tumor necrosis factor (TNF)-alpha stimulation and sprouted vessel-like structures in collagen I matrix. However, HCECs were slower to generate these sprouting vessels, when compared with HUVECs. The extent of inhibition of endothelial cell sprouting in 3D matrix, the blockade of TNF-alpha-induced IkappaB-alpha degradation, levels of global polyubiquitinated proteins, and induced production of HO-1 in response to treatment by the withanolides in cultured endothelial cells was similarly regulated between HCECs and HUVECs.
conclusionsHCECs share with HUVECs a similar response to UPP inhibitors, suggesting that this well-conserved pathway that regulates angioinflammatory mechanisms could be exploited for drug-targeting in the development of novel agents for CNV treatment.
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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.