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

The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells. To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot analysis were conducted. 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 the total protein level of MMP-2 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-2/-9, the ATP binding site of mTOR and JNK1/2/3. 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.