Novel artemisinin derivative FO8643 with anti-angiogenic activity inhibits growth and migration of cancer cells via VEGFR2 signaling

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000843327800003&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.ejphar.2022.175158
eISSN
1879-0712
Externe Identifier
  • Clarivate Analytics Document Solution ID: 3X9BL
  • PubMed Identifier: 35878807
ISSN
0014-2999
Zeitschrift
EUROPEAN JOURNAL OF PHARMACOLOGY
Schlüsselwörter
  • Artemisinin derivative
  • VEGFR2 signaling
  • Cell growth
  • Cell migration
  • Angiogenesis
  • Targeted cancer therapy
Artikelnummer
ARTN 175158
Datum der Veröffentlichung
2022
Status
Published
Titel
Novel artemisinin derivative FO8643 with anti-angiogenic activity inhibits growth and migration of cancer cells via VEGFR2 signaling
Sub types
  • Article
Ausgabe der Zeitschrift
930

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
DOI
10.1016/j.ejphar.2022.175158
ISSN
0014-2999
Zeitschrift
European Journal of Pharmacology
Sprache
en
Artikelnummer
175158
Paginierung
175158 - 175158
Datum der Veröffentlichung
2022
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.ejphar.2022.175158
Datum der Datenerfassung
2024
Titel
Novel artemisinin derivative FO8643 with anti-angiogenic activity inhibits growth and migration of cancer cells via VEGFR2 signaling
Ausgabe der Zeitschrift
930

Data source: Crossref

Abstract
The vascular endothelial growth factor receptor 2 (VEGFR2) is widely recognized as a key effector in angiogenesis and cancer progression and has been considered a critical target for the development of anti-cancer drugs. Artemisinin (ARS) and its derivatives exert profound efficacy in treating not only malaria but also cancer. As a novel ARS-type compound, FO8643 caused significant suppression of the growth of a panel of cancer cells, including both solid and hematologic malignancies. In CCRF-CEM leukemia cells, FO8643 dramatically inhibited cell proliferation coupled with increased apoptosis and cell cycle arrest. Additionally, FO8643 restrained cell migration in the 2D wound healing assay as well as in a 3D spheroid model of human hepatocellular carcinoma HUH-7 cells. Importantly, SwissTargetPrediction predicted VEGFR2 as an underlying target for FO8643. Molecular docking simulation further indicated that FO8643 formed hydrogen bonds and hydrophobic interactions within the VEGFR2 kinase domain. Moreover, FO8643 directly inhibited VEGFR2 kinase activity and its downstream action including MAPK and PI3K/Akt signaling pathways in HUH-7 cells. Encouragingly, FO8643 decreased angiogenesis in the chorioallantoic membrane assay in vivo. Collectively, FO8643 is a novel ARS-type compound exerting potential VEGFR2 inhibition. FO8643 may be a viable drug candidate in cancer therapy.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128, Mainz, Germany.
Autoren
DOI
10.1016/j.ejphar.2022.175158
eISSN
1879-0712
Externe Identifier
  • PubMed Identifier: 35878807
Funding acknowledgements
  • China Scholarship Council:
Open access
false
ISSN
0014-2999
Zeitschrift
European journal of pharmacology
Schlüsselwörter
  • Humans
  • Neoplasms
  • Neovascularization, Pathologic
  • Artemisinins
  • Vascular Endothelial Growth Factor Receptor-2
  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Cell Proliferation
  • Cell Movement
  • Phosphatidylinositol 3-Kinases
  • Human Umbilical Vein Endothelial Cells
  • Molecular Docking Simulation
Sprache
eng
Medium
Print-Electronic
Online publication date
2022
Paginierung
175158
Datum der Veröffentlichung
2022
Status
Published
Datum der Datenerfassung
2022
Titel
Novel artemisinin derivative FO8643 with anti-angiogenic activity inhibits growth and migration of cancer cells via VEGFR2 signaling.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
930

Data source: Europe PubMed Central

Abstract
The vascular endothelial growth factor receptor 2 (VEGFR2) is widely recognized as a key effector in angiogenesis and cancer progression and has been considered a critical target for the development of anti-cancer drugs. Artemisinin (ARS) and its derivatives exert profound efficacy in treating not only malaria but also cancer. As a novel ARS-type compound, FO8643 caused significant suppression of the growth of a panel of cancer cells, including both solid and hematologic malignancies. In CCRF-CEM leukemia cells, FO8643 dramatically inhibited cell proliferation coupled with increased apoptosis and cell cycle arrest. Additionally, FO8643 restrained cell migration in the 2D wound healing assay as well as in a 3D spheroid model of human hepatocellular carcinoma HUH-7 cells. Importantly, SwissTargetPrediction predicted VEGFR2 as an underlying target for FO8643. Molecular docking simulation further indicated that FO8643 formed hydrogen bonds and hydrophobic interactions within the VEGFR2 kinase domain. Moreover, FO8643 directly inhibited VEGFR2 kinase activity and its downstream action including MAPK and PI3K/Akt signaling pathways in HUH-7 cells. Encouragingly, FO8643 decreased angiogenesis in the chorioallantoic membrane assay in vivo. Collectively, FO8643 is a novel ARS-type compound exerting potential VEGFR2 inhibition. FO8643 may be a viable drug candidate in cancer therapy.
Date of acceptance
2022
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/35878807
DOI
10.1016/j.ejphar.2022.175158
eISSN
1879-0712
Zeitschrift
Eur J Pharmacol
Schlüsselwörter
  • Angiogenesis
  • Artemisinin derivative
  • Cell growth
  • Cell migration
  • Targeted cancer therapy
  • VEGFR2 signaling
  • Angiogenesis Inhibitors
  • Artemisinins
  • Cell Movement
  • Cell Proliferation
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Molecular Docking Simulation
  • Neoplasms
  • Neovascularization, Pathologic
  • Phosphatidylinositol 3-Kinases
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
Sprache
eng
Country
Netherlands
Paginierung
175158
PII
S0014-2999(22)00419-8
Datum der Veröffentlichung
2022
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Titel
Novel artemisinin derivative FO8643 with anti-angiogenic activity inhibits growth and migration of cancer cells via VEGFR2 signaling.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
930

Data source: PubMed

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