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

Autor: Mousavi, Seyed Hadi, Jalili-Nik, Mohammad, Soukhtanloo, Mohammad, Soltani, Arash, Abbasinezhad-Moud, Farzaneh, Mollazadeh, Hamid, Shakeri, Farzaneh, Bibak, Bahram, Sahebkar, Amirhossein, Afshari, Amir R.
Předmět:
Zdroj: Avicenna Journal of Phytomedicine; May/Jun2024, Vol. 14 Issue 3, p349-364, 16p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index