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

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

doi:10.22038/ajp.2023.23586

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

Document Type : Original Research Article

Authors

Seyed Hadi Mousavi ¹

Mohammad Jalili-Nik ²

Mohammad Soukhtanloo ²

Arash Soltani ²

Farzaneh Abbasinezhad-Moud ³

Hamid Mollazadeh ⁴

Farzaneh Shakeri ⁴

Bahram Bibak ⁴

Amirhossein Sahebkar ⁵

Amir R. Afshari ⁴

¹ Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

² Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

³ Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

⁴ Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical ‎Sciences, Bojnurd, Iran

⁵ Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India

10.22038/ajp.2023.23586

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 analysis 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 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.
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.

Keywords

Auraptene

Glioblastoma multiforme

Migration

Invasion

Metastasis

Subjects