Cucurbitacin-B inhibits cancer cell migration by targeting mortalin and HDM2: computational and
            <i>in vitro</i>
            experimental evidence

Huifu, He; Shefrin, Seyad; Yang, Shi Chun; Zhang, Zhenya; Kaul, Sunil C.; Sundar, Durai; Wadhwa, Renu

doi:10.1080/07391102.2023.2206914

Cited by 1 publication

(2 citation statements)

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“…shown that CuB has anti-migration ability in cancer cell lines (Huifu et al, 2023;Kaewmeesri et al, 2022). Although anti-migration activity seems to be due to inhibition of STAT3 and enhancement of STAT1 signaling, our results suggest that the reason could be binding G-actin (Guo et al, 2018).…”

Section: Discussionmentioning

confidence: 65%

“…Besides, the F‐actin polymerization rate was analyzed and compared with the other actin‐binding drugs, jasplakinolide and cytochalasin D, and it has been realized that CuI (200 nM) reduced the polymerization rate of F‐actin nearly as much as jasplakinolide and cytochalasin D. In our study, the formation of large cytoplasmic actin aggregates was observed in HUVECs by fluorescence microscopy, similar to Kenecht's study (Knecht et al., 2010 ). Recent studies have shown that CuB has anti‐migration ability in cancer cell lines (Huifu et al., 2023 ; Kaewmeesri et al., 2022 ). Although anti‐migration activity seems to be due to inhibition of STAT3 and enhancement of STAT1 signaling, our results suggest that the reason could be binding G‐actin (Guo et al., 2018 ).…”

Section: Discussionmentioning

confidence: 99%

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

Haciosmanoglu Aldogan,

Önsü,

Saylan

et al. 2023

Food Science & Nutrition

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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.

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Section: Discussionmentioning

confidence: 65%