DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway

IntroductionGliomas, particularly glioblastomas (GBM), are highly aggressive with a poor prognosis and low survival rate. Currently, deoxyelephantopin (DET) has shown promising anti-inflammatory and anti-tumor effects. Using clinical prognostic analysis, molecular docking, and network pharmacology,...

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Main Authors: Rui Zhao, Mengran Wang, Zeyu Wu, Panpan Zhao, Huiling Dong, Yue Su, Chenghui Zhao, Min Qi, Shizhang Ling, Xiaochun Jiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1528454/full
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author Rui Zhao
Mengran Wang
Zeyu Wu
Panpan Zhao
Huiling Dong
Yue Su
Chenghui Zhao
Min Qi
Shizhang Ling
Shizhang Ling
Xiaochun Jiang
Xiaochun Jiang
author_facet Rui Zhao
Mengran Wang
Zeyu Wu
Panpan Zhao
Huiling Dong
Yue Su
Chenghui Zhao
Min Qi
Shizhang Ling
Shizhang Ling
Xiaochun Jiang
Xiaochun Jiang
author_sort Rui Zhao
collection DOAJ
description IntroductionGliomas, particularly glioblastomas (GBM), are highly aggressive with a poor prognosis and low survival rate. Currently, deoxyelephantopin (DET) has shown promising anti-inflammatory and anti-tumor effects. Using clinical prognostic analysis, molecular docking, and network pharmacology, this study aims to explore the primary targets and signaling pathways to identify novel GBM treatment approaches.MethodsUsing PharmMapper, the chemical structure of DET was examined for possible targets after being acquired from PubChem. GBM-related targets were obtained through multi-omics approaches. A protein-protein interaction (PPI) network was constructed using Cytoscape and STRING, and target binding was evaluated through molecular docking. Enrichment analysis was conducted using Metascape. The effects of DET on GBM cell invasion, apoptosis, and proliferation were assessed through in vitro assays, including Transwell, EDU, CCK8, and flow cytometry. Western blot analysis was performed to examine the components of the PI3K/AKT signaling pathway.ResultsAmong the sixty-four shared targets identified, JUN and CCND1 were the most frequently observed. Enrichment analysis demonstrated that DET influenced the MAPK and PI3K/AKT signaling pathways. In Transwell assays, DET significantly inhibited the invasive behavior of glioma cells. Western blot analysis further confirmed the downregulation of EGFR, JUN, and PI3K/AKT.ConclusionDET inhibits GBM cell invasion, proliferation, and apoptosis via modulating the PI3K/AKT signaling pathway, highlighting its potential as a novel therapeutic strategy for GBM treatment.
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spelling doaj-art-c83978b3d5e74e2fa7948f20a3f4fe072025-01-09T14:18:15ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.15284541528454DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathwayRui Zhao0Mengran Wang1Zeyu Wu2Panpan Zhao3Huiling Dong4Yue Su5Chenghui Zhao6Min Qi7Shizhang Ling8Shizhang Ling9Xiaochun Jiang10Xiaochun Jiang11The Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Institutes of Brain Science, Wannan Medical College, Higher Education Park, Wuhu, Anhui, ChinaThe Translational Research Institute for Neurological Disorders of Wannan Medical College, Department of Neurosurgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, ChinaThe Institutes of Brain Science, Wannan Medical College, Higher Education Park, Wuhu, Anhui, ChinaIntroductionGliomas, particularly glioblastomas (GBM), are highly aggressive with a poor prognosis and low survival rate. Currently, deoxyelephantopin (DET) has shown promising anti-inflammatory and anti-tumor effects. Using clinical prognostic analysis, molecular docking, and network pharmacology, this study aims to explore the primary targets and signaling pathways to identify novel GBM treatment approaches.MethodsUsing PharmMapper, the chemical structure of DET was examined for possible targets after being acquired from PubChem. GBM-related targets were obtained through multi-omics approaches. A protein-protein interaction (PPI) network was constructed using Cytoscape and STRING, and target binding was evaluated through molecular docking. Enrichment analysis was conducted using Metascape. The effects of DET on GBM cell invasion, apoptosis, and proliferation were assessed through in vitro assays, including Transwell, EDU, CCK8, and flow cytometry. Western blot analysis was performed to examine the components of the PI3K/AKT signaling pathway.ResultsAmong the sixty-four shared targets identified, JUN and CCND1 were the most frequently observed. Enrichment analysis demonstrated that DET influenced the MAPK and PI3K/AKT signaling pathways. In Transwell assays, DET significantly inhibited the invasive behavior of glioma cells. Western blot analysis further confirmed the downregulation of EGFR, JUN, and PI3K/AKT.ConclusionDET inhibits GBM cell invasion, proliferation, and apoptosis via modulating the PI3K/AKT signaling pathway, highlighting its potential as a novel therapeutic strategy for GBM treatment.https://www.frontiersin.org/articles/10.3389/fonc.2024.1528454/fullgliomacell proliferationcell apoptosisPl3Kcell invasion
spellingShingle Rui Zhao
Mengran Wang
Zeyu Wu
Panpan Zhao
Huiling Dong
Yue Su
Chenghui Zhao
Min Qi
Shizhang Ling
Shizhang Ling
Xiaochun Jiang
Xiaochun Jiang
DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway
Frontiers in Oncology
glioma
cell proliferation
cell apoptosis
Pl3K
cell invasion
title DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway
title_full DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway
title_fullStr DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway
title_full_unstemmed DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway
title_short DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway
title_sort det induces apoptosis and suppresses tumor invasion in glioma cells via pi3k akt pathway
topic glioma
cell proliferation
cell apoptosis
Pl3K
cell invasion
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1528454/full
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