ArticleOncotarget2017
Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Targeting SUMOylation in glioblastoma: A novel avenue for therapy and biomarker discovery.Genes & diseases · 2026Review
- Post-translational modifications at the crossroads of cancer metabolism and immune regulation: therapeutic opportunities and challenges.International journal of surgery (London, England) · 2026Review
- Natural products against tau hyperphosphorylation-induced aggregates: Potential therapies for Alzheimer's disease.Archiv der Pharmazie · 2025Review
- Ginkgolic acid regulates myogenic development by influencing the proliferation and differentiation of C2C12 myoblast cells.Molecular medicine reports · 2024Article
- Targeted inhibition of SUMOylation: treatment of tumors.Human cell · 2024Review
- Exploring potential targets for natural product therapy of DN: the role of SUMOylation.Frontiers in pharmacology · 2024Review
- Article
- SUMOylation of PDGF receptor α affects signaling via PLCγ and STAT3, and cell proliferation.BMC molecular and cell biology · 2023Article
- Pharmacological Activities of Ginkgolic Acids in Relation to Autophagy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- In Silico and In Vitro Screening of 50 Curcumin Compounds as EGFR and NF-κB Inhibitors.International journal of molecular sciences · 2022Article
- Structure-Activity Relationship of Synthetic Ginkgolic Acid Analogs for Treating Type 2 Diabetes by PTPN9 Inhibition.International journal of molecular sciences · 2022Article
- SUMOylation regulates Rb hyperphosphorylation and inactivation in uveal melanoma.Cancer science · 2022Article
- SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.Frontiers in cell and developmental biology · 2022Review
- Ginkgolic acid promotes inflammation and macrophage apoptosisFrontiers in medicine · 2022Article
- Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90.Molecules (Basel, Switzerland) · 2021Article
- Niche specificity and functional diversity of the bacterial communities associated with Ginkgo biloba and Panax quinquefolius.Scientific reports · 2021Article
- Identification and characterization of deschloro-chlorothricin obtained from a large natural product library targeting aurora A kinase in multiple myeloma.Investigational new drugs · 2021Article
- Natural Salicylates and Their Roles in Human Health.International journal of molecular sciences · 2020Review
- Synthesis and Evaluation of Ginkgolic Acid Derivatives as SUMOylation Inhibitors.ACS medicinal chemistry letters · 2020Article
- Cytotoxic effect ofHeliyon · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ginkgolic acids (GA), a group of alkyl phenols found in crude extracts of Ginkgo biloba leaves, are known to have anticancer activity, but their mode of action is not well understood. Our aim in this study was to investigate the anti-migratory activity of seven GA against breast cancer cells and to determine the molecular mechanism behind this activity. All seven GA and their mixture inhibited wound healing in MCF-7 and MDA-MB 231 breast cancer cells. None of the compounds nor the mixture showed cytotoxicity towards the two cell lines, if tested by the resazurin assay. C13:0 inhibited NF-κB activity in the HEK Blue Null 1 reporter cell line. Furthermore, C13:0 inhibited degradation of nuclear factor of κ-light polypeptide gene enhancer in B-cells inhibitor α (IκBα). Sumoylation assay revealed that GA inhibited sumoylation of NF-κB essential modulator (NEMO). Molecular docking on SUMO-activating enzyme E1 showed that the seven GA bound to the active adenylation site with high calculated affinities ranging from -10.28 to -12.27 kcal/mol. Quantitative RT-PCR using C15:0, C13:0 and the mixture showed a significant down-regulation of urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinase 9 (MMP-9). We conclude that GA revealed considerable anti-migratory activity at non-cytotoxic concentrations, indicating anti-metastatic activity with low toxicity. This effect can be explained by the inhibition of NEMO sumoylation leading to inhibition of IκBα degradation and consequently a reduction of NF-κB activity, leading to the down-regulation of metastasis related genes including uPA, PAI-1, CXCR4, and MMP-9.
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Registered trials
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