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 exp...
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| Vydáno v: | Avicenna journal of phytomedicine Ročník 14; číslo 3; s. 349 - 364 |
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| Hlavní autoři: | , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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Iran
Mashhad University of Medical Sciences
01.05.2024
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| ISSN: | 2228-7930, 2228-7949 |
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| Abstract | 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 experiments 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 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.
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. |
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| AbstractList | 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 experiments 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 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.
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. The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells.ObjectiveThe 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 experiments were conducted.Materials and MethodsTo test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot experiments 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 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.ResultsAt 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.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.ConclusionAuraptene inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities. 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. |
| Author | Mollazadeh, Hamid Mousavi, Seyed Hadi Soltani, Arash Abbasinezhad-Moud, Farzaneh Jalili-Nik, Mohammad Soukhtanloo, Mohammad Afshari, Amir R Shakeri, Farzaneh Bibak, Bahram Sahebkar, Amirhossein |
| AuthorAffiliation | 7 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran 5 Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India 1 Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran 4 Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran 3 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran 2 Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 6 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran |
| AuthorAffiliation_xml | – name: 1 Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran – name: 5 Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India – name: 3 Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran – name: 2 Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran – name: 6 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran – name: 4 Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran – name: 7 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran |
| Author_xml | – sequence: 1 givenname: Seyed Hadi surname: Mousavi fullname: Mousavi, Seyed Hadi organization: Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran – sequence: 2 givenname: Mohammad surname: Jalili-Nik fullname: Jalili-Nik, Mohammad organization: Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran – sequence: 3 givenname: Mohammad surname: Soukhtanloo fullname: Soukhtanloo, Mohammad organization: Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran – sequence: 4 givenname: Arash surname: Soltani fullname: Soltani, Arash organization: Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran – sequence: 5 givenname: Farzaneh surname: Abbasinezhad-Moud fullname: Abbasinezhad-Moud, Farzaneh organization: Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran – sequence: 6 givenname: Hamid surname: Mollazadeh fullname: Mollazadeh, Hamid organization: Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran – sequence: 7 givenname: Farzaneh surname: Shakeri fullname: Shakeri, Farzaneh organization: Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran – sequence: 8 givenname: Bahram surname: Bibak fullname: Bibak, Bahram organization: Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran – sequence: 9 givenname: Amirhossein surname: Sahebkar fullname: Sahebkar, Amirhossein organization: Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran – sequence: 10 givenname: Amir R surname: Afshari fullname: Afshari, Amir R organization: Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran |
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| Keywords | Auraptene Metastasis Glioblastoma multiforme Migration Invasion |
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| Snippet | The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells.
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| SubjectTerms | auraptene glioblastoma multiforme invasion metastasis migration Original |
| Title | Auraptene inhibits migration, invasion and metastatic behavior of human malignant glioblastoma cells: An in vitro and in silico study |
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