Beauvericin Inhibits the Growth of U251 Glioma Cells and Promotes Apoptosis In Vitro

2020 ◽  
Vol 14 (5) ◽  
pp. 639-644
Author(s):  
Liming Hu ◽  
Tianyi Zhao ◽  
Jia Wang ◽  
Renguang Wang ◽  
Hongshi Bu ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
U251 Cell ◽  
Western Blot Assay ◽  
Expression Levels ◽  
Signal Transduction Proteins

To elucidated the inhibitory effect of beauvericin (BEA) on glioma cells and its possible molecular mechanism, in this study, the MTT assay was performed to observed the effect of BEA on cell proliferation, the flow cytometry was used to measure its protective effect on cell apoptosis, and the Western Blot assay was performed to test the expression levels of signal transduction proteins. In the results, the concentration of BEA was 0.5 μmoL/L in the drug group, indicating that it has obvious protect effect to the U251 cells. The apoptosis rates of BEA, Cis and BEA+Cis groups, compared with the U251 group, were 2.93, 3.71 and 5.0 times higher respectively. In addition, the expression levels of Cyclin D1, E, B and Bcl-2 in BEA group were 75, 69, 78 and 67% of that in the U251 group, while Bax and cleaved caspase-3 were twice as much as that in the U251 group. In conclusion, beauvericin can inhibit U251 cell apoptosis and the possible mechanism is to reduce the expression of Cyclin D1, B, E and Bcl-2, while the levels of Bax and cleaved Caspase-3 increased. Thus, BEA has a broad application prospect in the treatment of glioma.

Anti-glioma Efficacy and Mechanism of Action of Tripolinolate A from Tripolium pannonicum

Planta Medica ◽  
2018 ◽  
Vol 84 (11) ◽  
pp. 786-794
Author(s):  
Weiyun Chai ◽  
Lu Chen ◽  
Xiao-Yuan Lian ◽  
Zhizhen Zhang
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Cell Cycle Regulators ◽  
Expression Levels ◽  
Multiple Tumor ◽  
Glioma Growth

AbstractTripolinolate A as a new bioactive phenolic ester was previously isolated from a halophyte of Tripolium pannonicum. However, the in vitro and in vivo anti-glioma effects and mechanism of tripolinolate A have not been investigated. This study has demonstrated that (1) tripolinolate A inhibited the proliferation of different glioma cells with IC50 values of 7.97 to 14.02 µM and had a significant inhibitory effect on the glioma growth in U87MG xenograft nude mice, (2) tripolinolate A induced apoptosis in glioma cells by downregulating the expressions of antiapoptotic proteins and arrested glioma cell cycle at the G2/M phase by reducing the expression levels of cell cycle regulators, and (3) tripolinolate A also remarkably reduced the expression levels of several glioma metabolic enzymes and transcription factors. All data together suggested that tripolinolate A had significant in vitro and in vivo anti-glioma effects and the regulation of multiple tumor-related regulators and transcription factors might be responsible for the activities of tripolinolate A against glioma.

Biological and Molecular Evidences for the Antitumor Potential of EGb 761 in Glioma Cells In Vitro and In Vivo

2021 ◽  
Vol 15 (5) ◽  
pp. 685-692
Author(s):  
Xin Sui ◽  
Jia Zhou ◽  
Yan Xu ◽  
Yuchen Wang ◽  
Guangfu Lv ◽  
...  
Keyword(s):  
Growth Factor ◽  
Caspase 3 ◽  
Glioma Cells ◽  
Signalling Pathway ◽  
Migration And Invasion ◽  
Egb 761 ◽  
Western Blots ◽  
Expression Levels

EGb 761, the standardized extract from the Ginkgo biloba leaves, has therapeutic effect on many diseases. However, its mechanisms on glioma remain to be fully established. This study aims to investigate the possible effects of EGb 761 on glioma cells, to explore its potential mechanism. The glioma cells SHG44 and U251 were used as materials, the proliferation, migration and invasion were assessed by the MTT, the scratch-wound and Transwell assays were performed respectively. Levels of insulin-like growth factor-1, Bcl-2, p53, Smad2/3, Bax, cleaved caspase-3 and p-Smad2/3 were determined by western blots. The development and progression of U251 glioma cell were measured in vivo, and the apoptosis was evaluated. The results showed that EGb 761 could inhibit the proliferation, migration, and invasion of SHG-44 and U251 cells in vitro. Meanwhile, the expression levels of IGF-1 and Bcl-2, and the transforming growth factor-β (TGF-β) signaling were inhibited. In contrast, the expression levels of p53, Bax, and cleaved caspase-3 were increased significantly. In conclusion, this study suggested that EGb 761 could suppress the growth of glioma cells in vitro and in vivo, possibly by inhibiting the TGF-β signalling pathway and activating the p53 signalling pathway.

scholarly journals Tetramethylpyrazine Inhibits Activation of Hepatic Stellate Cells through Hedgehog Signaling Pathways In Vitro

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Jue Hu ◽  
Gang Cao ◽  
Xin Wu ◽  
Hao Cai ◽  
Baochang Cai
Keyword(s):  
Cyclin D1 ◽  
Hepatic Fibrosis ◽  
Hedgehog Signaling ◽  
Stellate Cell ◽  
Inhibitory Effect ◽  
Tissue Growth ◽  
Cyclin Dependent Kinase ◽  
Western Blot Assay ◽  
Cyclin E1

Background and Aim. Tetramethylpyrazine (TMP), a major alkaloid isolated fromLigusticum chuanxiong, has been reported in hepatic fibrosis models. However, the action mechanism remains unclear. In the present study, effects of tetramethylpyrazine (TMP) against hepatic stellate cell (HSC) activation as well as the possible mechanisms were evaluated.Methods. Western blot assay was used to detect TMP effects on protein expression of Smo, Patched, Hhip, and Gli and to investigate the effects of TMP on Cyclin D1, Cyclin E1, CDK2, Bcl-2, Bax, and caspase expression with cyclopamine supplementation.Results. Our results showed that TMP significantly inhibits the expression of Cyclin D1, Cyclin E1, and Cyclin-dependent kinase CDK2 and changes the HSC cycle by inhibiting the proliferation of HSC. Moreover, TMP has also been shown to decrease the expression of Bcl-2 and increase the expression of Bax in HSC-T6 cells. Furthermore, TMP can inhibit the expression of connective tissue growth factor (CTGF), and the inhibitory effect was intensified after the application of joint treatment with TMP and cyclopamine.Conclusion. TMP may be an effective Hh signaling pathway inhibitor for hepatic fibrosis treatment.

scholarly journals Protective effect of EGb761 against Aβ1-42 -induced SHSY5Y cells injury and blood-brain barrier disruption via regulating Akt/Nrf2 signaling pathway

2021 ◽  
Vol 20 (9) ◽  
pp. 1811-1818
Author(s):  
Liling Wang ◽  
Jianhua Mi ◽  
Yeping Song ◽  
Pengfei Wang
Keyword(s):  
Blood Brain Barrier ◽  
Cell Apoptosis ◽  
In Vitro Model ◽  
Caspase 3 ◽  
Cell Injury ◽  
Protective Role ◽  
Ros Generation ◽  
Expression Levels ◽  
Vitro Model

Purpose: Alzheimer’s disease (AD) is a common disease in the world caused by deposition in the brain parenchyma, accumulation of beta amyloid which leads to the blood brain barrier (BBB) disruption. Regardless of enough progress in the treatment of AD, the principal mechanism of BBB injury is yet not clear.Methods: In this study we examined the impact of EGb761on Aβ 1-42-induced SH-SY5Y cells in vitro  model of AD. Cell viability was assessed by using MTT assay, flow cytometry was used to check the rate of cell apoptosis, ROS generation and BBB leakage was assessed by measuring the level of fluorescence in Aβ-induced SH-SY5Y cells using a reactive oxygen species kit assay and BBB permeability assay, and mRNA levels of Bax, Bcl-2, caspase-3 was measured by using RT-qPCR.  Furthermore, western blot analysis was used to measure the protein expressions of Akt, Nrf2 and HO-1 in Aβ 1-42-induced SH-SY5Y cells.Results: The effect of EGb761 was investigated on the cell apoptosis induced by Aβ 1-42 andgeneration of ROS and we found that EGb761 plays a protective role against cell injury induced by Aβ 1-42. Cell apoptosis and ROS generation in SH-SY5Y cells decreased significantly with the treatment of EGb761. Furthermore, BBB permeability reduced considerably when the cells treated with EGb761 and the expression levels of Caspase-3 and Bax decreased while that of Bcl-2 were markedly increased in the Aβ 1-42-induced SH-SY5Y cells. Also, an increased in expression levels of p-Akt, Nrf2 (nucleus) and HO-1 was observed with the treatment of EGb761 in Aβ 1-42-induced SH-SY5Y cells.Conclusion: It can be concluded from these results that EGb761 could play a protective role byinhibiting apoptosis and protect Aβ 1-42-induced cell injury in vitro model of AD via activating Akt/Nrf2signaling pathway. Our study suggested that EGb761 might be a therapeutic agent for the preventionand treatment of AD.

scholarly journals Ropivacaine inhibits proliferation, migration, and invasion while inducing apoptosis of glioma cells by regulating the SNHG16/miR-424-5p axis

2020 ◽  
Vol 15 (1) ◽  
pp. 988-999
Author(s):  
Rong Liu ◽  
Min Wu ◽  
Guiju Xu ◽  
Lu Ju ◽  
Jinhui Xiao ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Glioma Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Western Blot Assay ◽  
Expression Levels ◽  
Rna Immunoprecipitation ◽  
Apoptotic Effects ◽  
Nucleolar Rna

AbstractBackgroundRegional anesthesia has anti-proliferative and pro-apoptotic effects in various cancers. Therefore, the purpose of this study was to investigate the effects of ropivacaine on the proliferation, migration, invasion, and apoptosis of glioma cells in vitro.MethodsUnder ropivacaine stimulation conditions, proliferation, apoptosis, migration, and invasion of glioma cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), flow cytometry, and transwell assays, respectively. Western blot assay was employed to measure the protein expression levels in glioma cells. The expression levels of small nucleolar RNA host gene 16 (SNHG16) and miR-424-5p were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The interaction relationship between SNHG16 and miR-424-5p was predicted and confirmed using a bioinformatics database and dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays.ResultsAfter treatment with ropivacaine, proliferation, migration, and invasion were repressed while apoptosis was enhanced in glioma cells in a dose-depended manner. In addition, ropivacaine impeded SNHG16 expression in glioma cells. Importantly, overexpression of SNHG16 abolished the ropivacaine-induced effects on glioma cells. Analogously, knockdown of miR-424-5p counteracted the function of ropivacaine in glioma cells. We also found that SNHG16 bound to miR-424-5p and negatively regulated miR-424-5p expression in glioma cells. The rescue experiments indicated that ropivacaine might regulate glioma progression by targeting the SNHG16/miR-424-5p axis.ConclusionOur findings revealed the anti-tumor effects of ropivacaine in glioma by targeting the SNHG16/miR-424-5p axis. These data might extend the understanding of regulatory mechanisms by which ropivacaine could suppress glioma development.

scholarly journals Enhancing Anti-Tumoral Potential of CD-NHF by Modulating PI3K/Akt Axis in U87 Ex Vivo Glioma Model

2021 ◽  
Vol 22 (8) ◽  
pp. 3873
Author(s):  
Gabriel Luta ◽  
Mihail Butura ◽  
Adrian Tiron ◽  
Crina E. Tiron
Keyword(s):  
Cell Line ◽  
Ex Vivo ◽  
Glioma Cells ◽  
In Vitro Study ◽  
Immunofluorescent Staining ◽  
Expression Levels ◽  
Disease Diagnostics ◽  
Phosphorylated Akt ◽  
Significant Impairment

Background: In the latest years, there has been an increased interest in nanomaterials that may provide promising novel approaches to disease diagnostics and therapeutics. Our previous results demonstrated that Carbon-dots prepared from N-hydroxyphthalimide (CD-NHF) exhibited anti-tumoral activity on several cancer cell lines such as MDA-MB-231, A375, A549, and RPMI8226, while U87 glioma tumor cells were unaffected. Gliomas represent one of the most common types of human primary brain tumors and are responsible for the majority of deaths. In the present in vitro study, we expand our previous investigation on CD-NHF in the U87 cell line by adding different drug combinations. Methods: Cell viability, migration, invasion, and immunofluorescent staining of key molecular pathways have been assessed after various treatments with CD-NHF and/or K252A and AKTVIII inhibitors in the U87 cell line. Results: Association of an inhibitor strongly potentiates the anti-tumoral properties of CD-NHF identified by significant impairment of migration, invasion, and expression levels of phosphorylated Akt, p70S6Kinase, or by decreasing expression levels of Bcl-2, IL-6, STAT3, and Slug. Conclusions: Using simultaneously reduced doses of both CD-NHF and an inhibitor in order to reduce side effects, the viability and invasiveness of U87 glioma cells were significantly impaired.

Synergistic Apoptotic Effect of Naringenin on enhancing the Anti-Glioma Efficacy of Temozolomide in an in vitro Experimental Model

2021 ◽  
Vol 16 (10) ◽  
pp. 43-49
Author(s):  
Precilla S. Daisy ◽  
S. Kuduvalli Shreyas ◽  
R. Sathish ◽  
T.S. Anitha
Keyword(s):  
Drug Treatment ◽  
Caspase 3 ◽  
Treatment Strategies ◽  
Glioma Cells ◽  
C6 Glioma ◽  
Mitigation Strategies ◽  
Treatment Modalities ◽  
C6 Glioma Cells ◽  
Dependent Manner

Glioma is one of the most devastating and difficult-totreat brain tumors with a very poor prognosis. Despite the current treatment modalities, the overall survival rate is only 5% contributing to a high mortality rate. Nevertheless, of emerging treatment strategies, there is still a rising need for novel mitigation strategies to counteract glioma aggressiveness. One attempt towards this long-term goal was made in this study to reveal the combined efficacy of naringenin, a bioactive flavonoid on enhancing the anti-glioma potency of temozolomide in C6 glioma cells. The cytotoxic effect of temozolomide and naringenin, both individually and in combination was assessed by employing MTT assay. The synergistic effect of the drugs temozolomide and naringenin was determined by calculating the combination index. To confirm the presence of apoptotic changes in the cells at morphological level, acridine orange/ethidium bromide staining was performed. Further, the modulatory effects of the drugs on apoptotic genes, caspase-3 and BCL-2 were evaluated using quantitative real time-PCR. Interestingly, we found that the combinatorial drug treatment was in consensus and effectively inhibited the growth of C6 glioma cells in a dose-dependent manner. Furthermore, this combinatorial drug treatment significantly up-regulated the expression of the proapoptotic gene, caspase-3 and down-regulated the anti-apoptotic gene BCL-2 suggesting a shift of equilibrium towards apoptosis. Our findings suggest that naringenin can be employed as a potent drug to enhance the anti-glioma efficacy of temozolomide and could be therapeutically exploited for the management of glioma.

scholarly journals Targeting the EZH2-PPAR Axis Is a Potential Therapeutic Pathway for Pancreatic Cancer

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jilong Hu ◽  
Zhinan Zheng ◽  
Jia Lei ◽  
Yuxin Cao ◽  
Qiyun Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Synergistic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist ◽  
Combined Use

Enhancer of zeste homolog 2 (EZH2) is abnormally highly expressed in pancreatic cancer (PC). However, it is not ideal to treat PC by inhibiting EZH2. This study reported that the combined use of pan-peroxisome proliferator-activated receptor (PPAR) agonist could significantly improve the anti-PC effect of EZH2 inhibitor. In vitro, PC cell lines PANC-1 and AsPC-1 were cultured, and MTT and flow cytometry were performed to observe the effects of pan-PPAR agonist bezafibrate and EZH2 selective inhibitor GSK126 on cell viability and apoptosis. In vivo, CDXs of PANC-1 and AsPC-1 were established to observe the effects of bezafibrate and GSK126 on bearing tumors. Western blotting was performed to detect the protein expressions of H3K27me3, β-catenin, p-β-catenin, cyclin D1, c-Myc, and cleaved caspase 3 in vitro and in vivo. The results showed that bezafibrate significantly improved the effects of GSK126 on proliferation inhibition and apoptosis promotion in vitro and the growth suppression of CDX tumors in vivo. It also significantly enhanced the effects of GSK126 on upregulating the expression level of p-β-catenin and that of cleaved caspase 3 in vitro and in vivo. In parallel, downregulation of the expression levels of H3K27me3, β-catenin, cyclin D1, and c-Myc was also observed in vitro or in vivo. These results suggest that the combination of bezafibrate and GSK126 has synergistic effects on PC, and the molecular mechanism may be related to the enhanced inhibition of the Wnt/β-catenin signaling pathway. We believe that targeting the EZH2-PPAR axis is a potential therapeutic pathway for PC.

scholarly journals Haloperidol and Risperidone Induce Apoptosis Neuronal Cell : Invivo Study

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ester G Panserga ◽  
Cecep S Kristanto ◽  
Budi Pratiti ◽  
Patricia Wulandari
Keyword(s):  
Cell Apoptosis ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Total Percentage ◽  
White Rats ◽  
Male Wistar Rats ◽  
Group B

Abstract Introduction Antipsychotics are drugs that are widely prescribed for mental disorders, such as schizophrenia and psychosis. Recent in vitro studies show antipsychotics play a role in the initiation of neuronal cell apoptosis. This study aims to determine the effect of haloperidol and risperidone on neuronal cell apoptosis in Wistar white rats. Methods Male wistar rats aged 8 weeks (n = 30) were used in this study. Wistar rats were randomized into 6 groups. Group A: 5 wistar rats as a control without induced schizophrenia, aquades and drugs. Group B: 5 Wistar-induced psychotic mice (using 30 mg / kgBB ketamine, intraperitoneal injection for 5 days) and aquadest. Group C: 5 rats were induced psychotic and were given haloperidol or 0.05 mg / kgBB orally, for 28 days. Group D: 5 mice were induced psychotic and were given haloperidol 0.1 mg / kg orally, for 28 days. Group E: 5 mice were induced psychotic and were given risperidone 0.05 mg / kgBB orally, for 28 days. Group F: 5 mice were induced psychotic and given risperidone 0.1 mg / kgBB orally, for 28 days. Apoptosis of neuronal cells in the ventral tegmental area was assessed by caspase-3 immunohistochemistry. The colored area will be calculated as a total percentage using the imageJ program. Results Risperidone and haloperidol increase caspase-3 activity, but haloperidol increases caspase-3 activity more than risperidone. Conclussion Risperidone and haloperidol induce apoptosis of neuronal cells and tardive dyskinesia in Wistar rats with psychotic models.

Wnt signalling inhibits adipogenesis in orbital fibroblasts from patients with Graves’ orbitopathy

2021 ◽  
pp. bjophthalmol-2020-316898
Author(s):  
Sang Joon Jung ◽  
Yeon Jeong Choi ◽  
Tae Kwann Park ◽  
Sang Earn Woo ◽  
Bo-Yeon Kim ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Adipogenic Differentiation ◽  
Wnt Signalling ◽  
Dependent Manner ◽  
Expression Levels ◽  
Graves Orbitopathy ◽  
Orbital Fibroblast ◽  
Vitro Model ◽  
Orbital Fibroblasts

Background/AimsTo investigate the role of Wnt signalling in adipogenesis using an in vitro model of Graves’ orbitopathy (GO).MethodsOrbital fat was obtained from patients with GO and non-GO participants for primary orbital fibroblast (OF) culture. Expression levels of Wnt5a, Wnt10b, β-catenin, phospho-β-catenin and cyclin D1 were compared between GO and non-GO OFs. These expression levels were also determined during adipogenesis of GO and non-GO OFs. The effects of a stimulator and inhibitor of Wnt signalling on adipogenesis of GO and non-GO OFs were investigated.ResultsWestern blotting analysis showed significant reductions in β-catenin and cyclin D1 and significant enhancement of phospho-β-catenin in OFs from patients with GO, compared with OFs from non-GO participants (p<0.05). Expression of Wnt5a, Wnt10b, β-catenin and cyclin D1 in OFs was highest on day 0, and then gradually declined after induction of adipogenic differentiation. The expression levels of PPARγ, C/EBPα and C/EBPβ were reduced in Wnt stimulator-treated OFs in a dose-dependent manner. Oil red O staining confirmed that a stimulator of Wnt inhibited adipogenesis in GO OFs.ConclusionThese results indicate that Wnt signalling inhibits adipogenesis in OFs from patients with GO and non-GO participants. Further studies are required to examine the potential of Wnt signalling as a target for therapeutic strategies.

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