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

  • سال انتشار: 1403
  • محل انتشار: مجله گیاهان دارویی ابن سینا، دوره: 14، شماره: 3
  • کد COI اختصاصی: JR_AJP-14-3_007
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 216
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نویسندگان

Seyed Hadi Mousavi

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

Mohammad Jalili-Nik

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

Mohammad Soukhtanloo

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

Arash Soltani

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

Farzaneh Abbasinezhad-Moud

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

Hamid Mollazadeh

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

Farzaneh Shakeri

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

Bahram Bibak

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

Amirhossein Sahebkar

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Amir R. Afshari

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

چکیده

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

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