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

Ebru Haciosmanoglu Aldogan*, Kemal Alper Önsü, Cemil Can Saylan, Başak Günçer, Sefer Baday, Muhammet Bektaş

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Özet

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 <.001). This study reveals the molecular mechanisms of CuI in the regulation of actin dynamics by binding G-actin. More importantly, this study indicates a novel role of CuI as an actin-targeting drug by binding directly to G-actin and may contribute to the mode of action of CuI on anticancer activities.

Orijinal dilİngilizce
DergiFood Science and Nutrition
DOI'lar
Yayın durumuKabul Edilmiş/Basında - 2023

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Publisher Copyright:
© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.

Finansman

This work was supported by TUBITAK/2214‐A (Project Number: 1059B141400326) and the Scientific Research Foundation of Istanbul University (Project Number: 30522).

FinansörlerFinansör numarası
Istanbul Üniversitesi30522

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