Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity

Publication type:
Journal article
Metadata:
Autoren
  • Sami Hamdoun
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000402051700096&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.18632/oncotarget.16626
eISSN
1949-2553
Externe Identifier
  • Clarivate Analytics Document Solution ID: EV8RY
  • PubMed Identifier: 28402272
Ausgabe der Veröffentlichung
21
Zeitschrift
ONCOTARGET
Schlüsselwörter
  • breast cancer
  • ginkgo biloba
  • NEMO
  • NF-kappa B
  • sumoylation
Paginierung
35103 - 35115
Datum der Veröffentlichung
2017
Status
Published
Titel
Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity
Sub types
  • Article
Ausgabe der Zeitschrift
8

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Sami Hamdoun
  • Thomas Efferth
DOI
10.18632/oncotarget.16626
eISSN
1949-2553
Ausgabe der Veröffentlichung
21
Zeitschrift
Oncotarget
Sprache
en
Online publication date
2017
Paginierung
35103 - 35115
Datum der Veröffentlichung
2017
Status
Published
Herausgeber
Impact Journals, LLC
Herausgeber URL
http://dx.doi.org/10.18632/oncotarget.16626
Datum der Datenerfassung
2023
Titel
Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity
Ausgabe der Zeitschrift
8

Data source: Crossref

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.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Autoren
DOI
10.18632/oncotarget.16626
eISSN
1949-2553
Externe Identifier
  • PubMed Identifier: 28402272
  • PubMed Central ID: PMC5471038
Open access
true
ISSN
1949-2553
Ausgabe der Veröffentlichung
21
Zeitschrift
Oncotarget
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Breast Neoplasms
  • Salicylates
  • Plasminogen Activator Inhibitor 1
  • NF-kappa B
  • Receptors, CXCR4
  • Signal Transduction
  • Cell Movement
  • Gene Expression Regulation, Neoplastic
  • Models, Molecular
  • Female
  • I-kappa B Kinase
  • Matrix Metalloproteinase 9
  • Urokinase-Type Plasminogen Activator
  • Sumoylation
  • MCF-7 Cells
  • Molecular Docking Simulation
Sprache
eng
Medium
Print
Open access status
Open Access
Paginierung
35103 - 35115
Datum der Veröffentlichung
2017
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2017
Titel
Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
8

Files

http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=16626&path%5B%5D=58497 https://europepmc.org/articles/PMC5471038?pdf=render

Data source: Europe PubMed Central

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.
Date of acceptance
2017
Autoren
  • Sami Hamdoun
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/28402272
DOI
10.18632/oncotarget.16626
eISSN
1949-2553
Externe Identifier
  • PubMed Central ID: PMC5471038
Ausgabe der Veröffentlichung
21
Zeitschrift
Oncotarget
Schlüsselwörter
  • NEMO
  • NF-κB
  • breast cancer
  • ginkgo biloba
  • sumoylation
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • I-kappa B Kinase
  • MCF-7 Cells
  • Matrix Metalloproteinase 9
  • Models, Molecular
  • Molecular Docking Simulation
  • NF-kappa B
  • Plasminogen Activator Inhibitor 1
  • Receptors, CXCR4
  • Salicylates
  • Signal Transduction
  • Sumoylation
  • Urokinase-Type Plasminogen Activator
Sprache
eng
Country
United States
Paginierung
35103 - 35115
PII
16626
Datum der Veröffentlichung
2017
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2018
Titel
Ginkgolic acids inhibit migration in breast cancer cells by inhibition of NEMO sumoylation and NF-κB activity.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
8

Data source: PubMed

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