Biomarker Expression Profiling in Cervix Carcinoma Biopsies Unravels WT1 as a Target of Artesunate

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000887077500004&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.21873/cgp.20355
eISSN
1790-6245
Externe Identifier
  • Clarivate Analytics Document Solution ID: 6J8OJ
  • PubMed Identifier: 36316038
ISSN
1109-6535
Ausgabe der Veröffentlichung
6
Zeitschrift
CANCER GENOMICS & PROTEOMICS
Schlüsselwörter
  • Key Words
  • Chemotherapy
  • drug repurposing
  • natural products
  • sesquiterpenoids
Paginierung
727 - 739
Datum der Veröffentlichung
2022
Status
Published
Titel
Biomarker Expression Profiling in Cervix Carcinoma Biopsies Unravels WT1 as a Target of Artesunate
Sub types
  • Article
Ausgabe der Zeitschrift
19

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
DOI
10.21873/cgp.20355
eISSN
1790-6245
ISSN
1109-6535
Ausgabe der Veröffentlichung
6
Zeitschrift
Cancer Genomics - Proteomics
Sprache
en
Online publication date
2022
Paginierung
727 - 739
Datum der Veröffentlichung
2022
Status
Published
Herausgeber
Anticancer Research USA Inc.
Herausgeber URL
http://dx.doi.org/10.21873/cgp.20355
Datum der Datenerfassung
2022
Titel
Biomarker Expression Profiling in Cervix Carcinoma Biopsies Unravels WT1 as a Target of Artesunate
Ausgabe der Zeitschrift
19

Data source: Crossref

Abstract
<h4>Background/aim</h4>Artemisinin and its derivatives are not only approved antimalarial drugs but also exert strong anticancer activity. Based on the clinical activity of artesunate (ART) that has been previously reported in cervix carcinoma, we investigated a panel of 12 different biomarkers and identified the Wilms Tumor 1 (WT1) protein as a potential target of ART.<h4>Patients and methods</h4>Matched biopsies of cervical carcinoma before, during, and after therapy from patients treated with ART were investigated for induction of apoptosis (TUNEL assay) and expression of Wilms Tumor protein 1 (WT1), 14-3-3 ζ, cluster of differentiation markers (CD4, CD8, CD56), ATP-binding cassette transporter B5 (ABCB5), glutathione S-transferase P1 (GSTP1), inducible nitric oxide synthase (iNOS), translationally controlled tumor protein (TCTP), eukaryotic elongation factor 3 (eIF3), and ADP/ATP translocase by immunohistochemistry. WT1 has been selected for more detailed analyses using molecular docking in silico, microscale thermophoresis using recombinant WT1, and cytotoxicity testing (resazurin assay) using HEK293 cells transfected with four different WT1 splice variants.<h4>Results</h4>The fraction of apoptotic cells and the expression of WT1, 14-3-3 ζ, and CD4 increased upon ART treatment in tumors of patients. ART was bound in silico to a domain located at the DNA-binding site of WT1, while dihydroartemisinin (DHA) was bound with low affinity to a different site of WT1 not related to DNA-binding. The results were verified using microscale thermophoresis, where ART but not DHA bound to recombinant WT1. Transfectants overexpressing different WT1 splice variants exerted low but significant resistance to ART (≈2-fold).<h4>Conclusion</h4>WT1 may represent a novel target of ART in cancer cells that contribute to the response of tumor cells to this drug.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
Autoren
DOI
10.21873/cgp.20355
eISSN
1790-6245
Externe Identifier
  • PubMed Identifier: 36316038
  • PubMed Central ID: PMC9620444
Open access
false
ISSN
1109-6535
Ausgabe der Veröffentlichung
6
Zeitschrift
Cancer genomics & proteomics
Schlüsselwörter
  • Cervix Uteri
  • Humans
  • Carcinoma
  • WT1 Proteins
  • Biopsy
  • Female
  • HEK293 Cells
  • Molecular Docking Simulation
  • Biomarkers
  • Artesunate
Sprache
eng
Medium
Print
Paginierung
727 - 739
Datum der Veröffentlichung
2022
Status
Published
Datum der Datenerfassung
2022
Titel
Biomarker Expression Profiling in Cervix Carcinoma Biopsies Unravels WT1 as a Target of Artesunate.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
19

Files

https://cgp.iiarjournals.org/content/cgp/19/6/727.full.pdf https://europepmc.org/articles/PMC9620444?pdf=render

Data source: Europe PubMed Central

Abstract
BACKGROUND/AIM: Artemisinin and its derivatives are not only approved antimalarial drugs but also exert strong anticancer activity. Based on the clinical activity of artesunate (ART) that has been previously reported in cervix carcinoma, we investigated a panel of 12 different biomarkers and identified the Wilms Tumor 1 (WT1) protein as a potential target of ART. PATIENTS AND METHODS: Matched biopsies of cervical carcinoma before, during, and after therapy from patients treated with ART were investigated for induction of apoptosis (TUNEL assay) and expression of Wilms Tumor protein 1 (WT1), 14-3-3 ζ, cluster of differentiation markers (CD4, CD8, CD56), ATP-binding cassette transporter B5 (ABCB5), glutathione S-transferase P1 (GSTP1), inducible nitric oxide synthase (iNOS), translationally controlled tumor protein (TCTP), eukaryotic elongation factor 3 (eIF3), and ADP/ATP translocase by immunohistochemistry. WT1 has been selected for more detailed analyses using molecular docking in silico, microscale thermophoresis using recombinant WT1, and cytotoxicity testing (resazurin assay) using HEK293 cells transfected with four different WT1 splice variants. RESULTS: The fraction of apoptotic cells and the expression of WT1, 14-3-3 ζ, and CD4 increased upon ART treatment in tumors of patients. ART was bound in silico to a domain located at the DNA-binding site of WT1, while dihydroartemisinin (DHA) was bound with low affinity to a different site of WT1 not related to DNA-binding. The results were verified using microscale thermophoresis, where ART but not DHA bound to recombinant WT1. Transfectants overexpressing different WT1 splice variants exerted low but significant resistance to ART (≈2-fold). CONCLUSION: WT1 may represent a novel target of ART in cancer cells that contribute to the response of tumor cells to this drug.
Date of acceptance
2022
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/36316038
DOI
10.21873/cgp.20355
eISSN
1790-6245
Externe Identifier
  • PubMed Central ID: PMC9620444
Ausgabe der Veröffentlichung
6
Zeitschrift
Cancer Genomics Proteomics
Schlüsselwörter
  • Chemotherapy
  • drug repurposing
  • natural products
  • sesquiterpenoids
  • Female
  • Humans
  • Artesunate
  • Molecular Docking Simulation
  • HEK293 Cells
  • Cervix Uteri
  • Carcinoma
  • Biopsy
  • Biomarkers
  • WT1 Proteins
Sprache
eng
Country
Greece
Paginierung
727 - 739
PII
19/6/727
Datum der Veröffentlichung
2022
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Biomarker Expression Profiling in Cervix Carcinoma Biopsies Unravels WT1 as a Target of Artesunate.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
19

Data source: PubMed

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