Depolymerization of actin filaments by Cucurbitacin I through binding G‐actin

Cucurbitacins have high economic value as they are a major source of food and have pharmacological properties. Cucurbitacin I (CuI) is a plant‐derived natural tetracyclic triterpenoid compound that shows an anticancer effect via inhibiting the JAK2‐STAT3 signaling pathway. The actin cytoskeleton is...

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Bibliographic Details
Published in:Food science & nutrition 2024-02, Vol.12 (2), p.881-889
Main Authors: Haciosmanoglu Aldogan, Ebru, Önsü, Kemal Alper, Saylan, Cemil Can, Günçer, Başak, Baday, Sefer, Bektaş, Muhammet
Format: Article
Language:English
Subjects:
Actin
actin dynamics
Anticancer properties
Binding sites
Cancer
Cancer therapies
Cell adhesion & migration
Cell migration
cucurbitacin I
Cytoskeleton
Depolymerization
Endothelial cells
Filaments
Food sources
Free form
F‐actin
G‐actin
Herbal medicine
High temperature
Janus kinase 2
Ligands
Mode of action
Molecular modelling
Musculoskeletal system
Original
Pharmacology
Plants
Polymerization
Proteins
Signal transduction
Simulation
Software
Stat3 protein
target protein
Thermal stability
Variance analysis
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Summary:Cucurbitacins have high economic value as they are a major source of food and have pharmacological properties. Cucurbitacin I (CuI) is a plant‐derived natural tetracyclic triterpenoid compound that shows an anticancer effect via inhibiting the JAK2‐STAT3 signaling pathway. The actin cytoskeleton is the most abundant protein in cells and regulates critical events through reorganization in cells. In this study, it is aimed at determining the direct effect of CuI on actin dynamics. The fluorescence profile of G‐actin in the presence of CuI (1–200 nM) shifted to a higher temperature, suggesting that G‐actin binds CuI and that G‐actin–CuI is more thermally stable than the ligand‐free form. CuI dose‐dependently inhibited the polymerization of F‐actin in vitro and disrupted actin filaments in endothelial cells. Docking and MD simulations suggested that CuI binds to the binding site formed by residues I136, I175, D154, and A138 that are at the interface of monomers in F‐actin. The migration ability of cells treated with CuI for 24 h was significantly lower than the control group (p 
ISSN:2048-7177
2048-7177
DOI:10.1002/fsn3.3804