Auraptene inhibits migration, invasion and metastatic behavior of human malignant glioblastoma cells: An in vitro and in silico study.

IF 1.9 Q3 CHEMISTRY, MEDICINAL

Avicenna Journal of Phytomedicine Pub Date : 2024-05-01 DOI:10.22038/AJP.2023.23586

Seyed Hadi Mousavi, Mohammad Jalili-Nik, Mohammad Soukhtanloo, Arash Soltani, Farzaneh Abbasinezhad-Moud, Hamid Mollazadeh, Farzaneh Shakeri, Bahram Bibak, Amirhossein Sahebkar, Amir R Afshari

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Abstract

Objective: The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells.

Materials and methods: To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot experiments were conducted.

Results: At sublethal concentrations of 12.5 and 25 µg/ml, auraptene exhibited a significant reduction in cell invasion and migration of U87 cells, as assessed using scratch wound healing and Transwell tests, respectively. The qRT-PCR and zymography experiments demonstrated a significant decrease in both mRNA expression and activities of MMP-2 and MMP-9 following auraptene treatment. Western blot analysis also showed that MMP-2 protein level and phosphorylation of metastasis-related proteins (p-JNK and p-mTOR) decreased in auraptene-treated cells. Molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-2/-9, the ATP binding site of mTOR and JNK1/2/3.

Conclusion: Auraptene inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities.

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金合欢烯能抑制人类恶性胶质母细胞瘤细胞的迁移、侵袭和转移行为：一项体外和硅学研究。

目的：本研究探讨了痩素对 U87 多形性胶质母细胞瘤细胞的抗转移作用及其作用机制：本研究探讨了金合欢苷在 U87 多形性胶质母细胞瘤（GBM）细胞中的抗转移作用及其作用机制：为验证假设，进行了细胞培养、Matrigel侵袭试验、划痕伤口愈合试验、明胶酶谱分析、qRT-PCR和Western印迹实验：结果：在 12.5 和 25 µg/ml 的亚致死浓度下，金合欢烯能显著减少 U87 细胞的侵袭和迁移，分别通过划痕伤口愈合试验和 Transwell 试验进行评估。qRT-PCR 和酶谱分析实验表明，枳椇烯处理后，MMP-2 和 MMP-9 的 mRNA 表达和活性均显著下降。Western 印迹分析也显示，枳椇树素处理的细胞中 MMP-2 蛋白水平和转移相关蛋白（p-JNK 和 p-mTOR）的磷酸化程度均有所下降。分子对接研究一致表明，枳椇烯对 MMP-2/-9、mTOR 的 ATP 结合位点和 JNK1/2/3 具有显著的亲和力：结论：金萝庚烯可抑制GBM细胞的迁移和侵袭。这种抑制作用是通过调节特定机制（包括抑制 MMPs、JNK 和 mTOR 活性）而产生的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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