Arctigenin upregulates apoptosis through the AKT/MTOR pathway, inhibiting the proliferation of glioma

2019 ◽  
Author(s):  
jiang yongan ◽  
Liu Jia yu ◽  
Hong Wangwang ◽  
Fei Xiaowei ◽  
Liu ru'en
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Glioma Cells ◽  
Mtor Pathway ◽  
Migration And Invasion ◽  
Glioblastoma Cell ◽  
Caspase 9 ◽  
Arctium Lappa ◽  
Dose Dependent ◽  
Glioblastoma Cell Lines

Abstract Arctigenin (ARG) is a natural lignan compound extracted from arctium lappa and has displayed anticancer functions and effective treatments in a variety of cancers.Studies had shown that Arctigenin(ARG) inhibits tumors through the AKT/MTOR pathway and mediates autophagy.However,the role in glioma cellshave not still fully understood.This study was designed to investigate whether Arctigenin(ARG) can mediateAKT/mTOR pathway in glioma to regulate autophagy,and affected glioma cells growth and survival.We found that the dose-dependent downregulation of Arctigenin(ARG),reducing cell proliferation,migration and invasion in two human glioblastoma cell lines (U87, T98G),These phenomena were reversed after the administration of the AKT agonist (SC79). Arctigenin(ARG) also affected other autophagy markers such as p62, LC3B.In addition, the apoptotic molecules cleaved-PARP,caspase-9, and cleaved-caspase3 were also dose-dependently altered.

scholarly journals Arctigenin Inhibits Glioblastoma Proliferation through the AKT/mTOR Pathway and Induces Autophagy

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yong’an Jiang ◽  
Jiayu Liu ◽  
Wangwang Hong ◽  
Xiaowei Fei ◽  
Ru’en Liu
Keyword(s):  
Cell Cycle ◽  
Western Blotting ◽  
Glioma Cells ◽  
Annexin V ◽  
Mtor Pathway ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Arctium Lappa ◽  
Related Proteins ◽  
Dose Dependent

Purpose. Arctigenin (ARG) is a natural lignan compound extracted from Arctium lappa and has displayed anticancer function and therapeutic effect in a variety of cancers. Arctigenin is mainly from Arctium lappa extract. It has been shown to induce autophagy in various cancers. However, as for whether arctigenin induces autophagy in gliomas or not, the specific mechanism is still worth exploring. Methods. Using CCK8, the monoclonal experiment was made to detect the proliferation ability. The scratch experiment and the transwell experiment were applied to the migration and invasion ability. PI/RNase and FITC-conjugated anti-annexin V were used to detect the cell cycle and apoptosis. Western blotting was used to determine the specified protein level, and constructed LC3B-GFP plasmid was used for analysis of autophagy.Results. Our research showed that ARG inhibited the growth and proliferation and invasion and migration of glioma cells in a dose-dependent manner (U87MG and T98G) and arrested the cell cycle and induced apoptosis. Interestingly, ARG induced autophagy in a dose-dependent manner. We applied Western blotting to measure the increase in the key autophagy protein LC3B, as well as some other autophagy-related proteins (increase in Beclin-1 and decrease in P62). In order to further explore the mechanism that ARG passed initiating autophagy to inhibit cell growth, we further found by Western blotting that AKT and mTOR phosphorylation proteins (P-AKT, P-mTOR) were reduced after ARG treatment, and we used AKT agonists to rescue, and the phosphorylated proteins of AKT and mTOR increased, and we found that the autophagy-related proteins were also reversed. And interestingly, the protein of apoptosis was also reversed along with autophagy. Conclusions. We thought ARG inhibited the proliferation of glioma cells by inducing autophagy and apoptosis through the AKT/mTOR pathway.

Silencing of Eps8 blocks migration and invasion in human glioblastoma cell lines

2012 ◽  
Vol 318 (15) ◽  
pp. 1901-1912 ◽  
Author(s):  
Maria Grazia Cattaneo ◽  
Elisa Cappellini ◽  
Lucia M. Vicentini
Keyword(s):  
Cell Lines ◽  
Migration And Invasion ◽  
Glioblastoma Cell ◽  
Human Glioblastoma ◽  
Human Glioblastoma Cell ◽  
Glioblastoma Cell Lines

scholarly journals Smarcd1 Inhibits the Malignant Phenotypes of Human Glioblastoma Cells via Crosstalk with Notch1

2020 ◽  
Author(s):  
Yihao Zhu ◽  
Handong Wang ◽  
Maoxing Fei ◽  
Ting Tang ◽  
Wenhao Niu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
High Grade Glioma ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Protein Levels ◽  
Enhanced Expression ◽  
Human Glioblastoma Cells ◽  
Glioblastoma Cell Lines

AbstractSmarcd1 is a component of an evolutionary conserved chromatin remodeling complex—SWI/SNF, which is involved in transcription factor recruitment, DNA replication, recombination, and repair. Suppression of the SWI/SNF complex required for cellular differentiation and gene regulation may be inducible for cell proliferation and tumorigenicity. However, the inhibitory role of Smarcd1 in human glioblastoma cells has not been well illustrated. Both U87 and U251 human glioblastoma cell lines were employed in the present study. The lentivirus-mediated gene knockdown and overexpression approach was conducted to determine the function of Smarcd1. The protein levels were tested by western blot, and the relative mRNA contents were detected by quantitative real-time PCR. Cell viability was tested by CCK-8 and colony-forming assay. Transwell assays were utilized to evaluate the motility and invasive ability. Flow cytometry was employed to analyze cell cycle and apoptosis. SPSS software was used for statistical analysis. Low expression of Smarcd1 was observed in glioblastoma cell lines and in patients with high-grade glioma. Importantly, the depletion of Smarcd1 promoted cell proliferation, invasion, and chemoresistance, whereas enhanced expression of Smarcd1 inhibited tumor-malignant phenotypes. Mechanistic research demonstrated that overexpression of Smarcd1 decreased the expression of Notch1, while knockdown of Notch1 increased the expression of Smarcd1 through Hes1 suppression. Hence, the crosstalk between Smarcd1 and Notch1, which formed a feedback loop, was crucial in regulation of glioblastoma malignant phenotypes. Furthermore, targeting Smarcd1 could be a potential strategy for human glioblastoma treatment.

Differential effects of vincristine and phenytoin on the proliferation, migration, and invasion of human glioma cell lines

1995 ◽  
Vol 82 (6) ◽  
pp. 1035-1043 ◽  
Author(s):  
Jörg-Christian Tonn ◽  
Hans Kristian Haugland ◽  
Jaakko Saraste ◽  
Klaus Roosen ◽  
Ole Didrik Laerum
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Content Type ◽  
Glioma Cell Lines ◽  
Dose Dependent ◽  
Fine Print

✓ The aim of this study was to investigate the antimigratory and antiinvasive potential of vincristine sulfate (VCR) on human glioma cells and to analyze whether phenytoin (5,5-diphenylhydantoin; DPH) might act synergistically with VCR. Vincristine affects the cytoplasmic microtubules; DPH has been reported to enhance VCR cytotoxicity in murine cells. In two human glioma cell lines, GaMG and D-37MG, we found VCR to reduce monolayer growth and colony formation in a dose-dependent fashion at concentrations of 10 ng/ml and above. Phenytoin increased the cytotoxic and cystostatic effects of VCR in monolayer cells but not in spheroids. Multicellular spheroids were used to investigate directional migration. A coculture system of GaMG and D-37MG spheroids with fetal rat brain aggregates was used to analyze and quantify tumor cell invasion. A dose-dependent inhibition of migration and invasion by VCR was observed in both cell lines without further enhancement by DPH. Immunofluorescence microscopy with antibodies against α-tubulin revealed dose-dependent morphological alterations in the microtubules when the cells were exposed to VCR but not after incubation with DPH. Based on the combination of standardized in vitro model systems currently in use and the present data, the authors strongly suggest that VCR inhibits migration and invasion of human glioma cells. This is not altered by DPH, which inhibits cell proliferation in combination with VCR.

scholarly journals miR-548x and miR-4698 controlled cell proliferation by affecting the PI3K/AKT signaling pathway in Glioblastoma cell lines

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mohammad Reza kalhori ◽  
Ehsan Arefian ◽  
Fereshteh Fallah Atanaki ◽  
Kaveh Kavousi ◽  
Masoud Soleimani
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Glioblastoma Cell ◽  
Akt Signaling Pathway ◽  
Glioblastoma Cell Lines

Extracellular Vesicles Derived from Glioblastoma Promote Proliferation and Migration of Neural Progenitor Cells via PI3K-Akt Pathway

2021 ◽  
Author(s):  
Jiabin Pan ◽  
Shiyang Sheng ◽  
Ling Ye ◽  
Yizhao Ma ◽  
Lisha Qiu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Progenitor Cells ◽  
Cell Lines ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Mtor Pathway ◽  
Glioblastoma Cell ◽  
And Migration ◽  
Glioblastoma Cell Lines ◽  
Proliferation And Migration

Abstract BackgroundGlioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs’ alteration remain unkown. MethodsWe utilized two classic glioblastoma cell lines, U87- and A172, and collected EVs in the culture medium of those two lines. Mouse NPCs (mNPCs) were co-cultured with U87- or A172-derived EVs. EVs-treated mNPCs’ prolifeartion and migration were examined. Proteomic analysis and western-blot were utilized to identify the underlying mechanisms of glioblastoma EVs-induced alterations in mNPCs.ResultsWe show that glioblastoma cell lines U87- and A172-derived EVs dramatically promoted NPCs proliferation and migration. Mechanistic studies identify that EVs achieve their functions via activating PI3K-Akt-mTOR pathway in recipient cells. Inhibiting PI3K-Akt reversed the elevated prolfieration and migration of glioblastoma EVs-treated mNPCs. ConclusionOur findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy.

scholarly journals Knockdown of BCL6 Inhibited Malignant Phenotype and Enhanced Sensitivity of Glioblastoma Cells to TMZ through AKT Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Wen Song ◽  
Zhenling Wang ◽  
Pengcheng Kan ◽  
Zhuolin Ma ◽  
Yaru Wang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Mapk Signaling ◽  
Migration And Invasion ◽  
Phenotypic Change ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Protein Levels ◽  
Normal Tissues ◽  
Enhanced Sensitivity ◽  
Glioblastoma Cell Lines

Background. BCL6 was a critical prooncogene of human B-cell lymphomas which promoted tumor progress and contributed to malignant behavior in several kinds of cancers. This study was to detect the expression of BCL6 and its biological effect on glioma. Methods. RT-PCR and Western blot were used to detect the expression of BCL6 mRNA and protein in tissues and glioblastoma cell lines. The expression of BCL6 was knockdown in two glioblastoma cell lines (U87 and U251) using BCL6 shRNA. The CCK8, colony-formation, flow cytometry, Transwell, and wound-healing assays were used to evaluate the malignant phenotypic change of glioblastoma cells. Results. The expression of BCL6 was higher in glioma tissues and glioblastoma cell lines than normal tissues. Knockdown of BCL6 expression reduced the proliferation, migration, and invasion of glioblastoma cells. Moreover, knockdown of BCL6 changed expression of proteins related to malignant behaviors of glioblastoma cells. The suppression of BCL6 could increase chemosensitivity of U87 and U251 to temozolomide. Downregulation of BCL6 levels suppressed the expression of BCL2, cyclin D1, MMP2, and MMP9 proteins as well as two classic signaling pathway proteins p-AKT and p-ERK. Simultaneously, BAX and p21 protein levels were upregulated along with knockdown of BCL6. Conclusions. Our results indicated that BCL6 may be a tumor oncogene involved in the progression of glioma via affecting AKT and MAPK signaling pathways.

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