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

Objective: The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U۸۷ 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 analysis were conducted.Results: At sublethal concentrations of ۱۲.۵ and ۲۵ µg/ml, auraptene exhibited a significant reduction in cell invasion and migration of U۸۷ 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-۲ and MMP-۹ following auraptene treatment. Western blot analysis also showed that the total protein level of MMP-۲ as well as phosphorylation of crucial metastasis-related proteins, including p-JNK and p-mTOR, decreased in auraptene-treated cells. The molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-۲/-۹, the ATP binding site of mTOR and JNK۱/۲/۳.Conclusion: Auraptene effectively inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities. Auraptene might serve as a potential anti-metastatic agent against malignant GBM.

کلیدواژه ها:

Auraptene ، Glioblastoma multiforme ، Migration ، Invasion ، Metastasis