scholarly journals Bioactive compounds from Lactarius deterrimus interfere with the invasive potential of gastric cancer cells

2021 ◽  
Author(s):  
Kamila Król ◽  
Maciej Pudełek ◽  
Gracjana Krzysiek-Mączka ◽  
Mateusz Wierdak ◽  
Bożena Muszyńska ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioactive Compounds ◽  
Treatment Strategies ◽  
Cancer Therapies ◽  
Invasive Potential ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Phenolic Fraction ◽  
Atp Production ◽  
Cytoskeleton Rearrangements

Stomach cancer is the 4th most common cancer diagnosed worldwide. Despite intensive research on its etiopathology, its treatment strategies have not changed in the last 50 years. Mushrooms have recently attracted much attention as the source of bioactive compounds that can potentially complement cancer therapies. Here, we extracted a phenolic fraction from Lactarius deterrimus and analyzed its composition and bioactivity against the gastric cancer (AGS) cells. The complexity of L. deterrimus compounds was revealed by an HPLC assay, and was accompanied by cytostatic, cytotoxic and anti-invasive effects of the L. deterrimus extract (LDE). These are illustrated by inhibition of the AGS cells’ proliferation, metabolic activity and motility, and by induction of the cytoskeleton rearrangements. Apparently, these effects are exerted via activation of intracellular oxidative stress and decreased ATP production in AGS cells that could not be compensated by induction of autophagy. Less severe LDE effects were seen on physiology of normal gastric fibroblasts; however, inhibition of their motility indicates that LDE can interfere with gastric cancer development via an effect on stromal cells. Along with the observed synergy of LDE and cisplatin/5-fluorouracil effects on AGS cells, our data show the potential of LDE for supplementation of the gastric cancer therapy.

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

2020 ◽  
Vol 20 ◽  
Author(s):  
En Xu ◽  
Hao Zhu ◽  
Feng Wang ◽  
Ji Miao ◽  
Shangce Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dual Inhibitor ◽  
Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

scholarly journals M2 Macrophages Mediate the Resistance of Gastric Adenocarcinoma Cells to 5-Fluorouracil through the Expression of Integrin β3, Focal Adhesion Kinase, and Cofilin

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Daniel Ngabire ◽  
Irvine Niyonizigiye ◽  
Maheshkumar Prakash Patil ◽  
Yeong-Ae Seong ◽  
Yong Bae Seo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Focal Adhesion ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Alternatively Activated Macrophages ◽  
Adhesion Protein ◽  
Integrin Β3 ◽  
Cancer Invasiveness ◽  
Gastric Cancer Treatment ◽  
Focal Adhesion Protein

Tumor microenvironment components dictate the growth and progression of various cancers. Tumor-associated macrophages are the most predominant cells in TME and play a major role in cancer invasiveness. Gastric cancer is one of the most common cancers in Asia, and recently, various cases of resistance to fluorouracil treatment have been reported. In this study, we investigated the role of alternatively activated macrophages in the resistance of AGS gastric cancer cells to fluorouracil. THP-1 cells were polarized using recombinant human IL-4, then were cocultured with AGS cells treated with fluorouracil. Cell viability, Western blot, immunofluorescence, and cell invasion were performed for this investigation. Our results demonstrated that polarized macrophages initiated the survival of treated AGS cells and induced the resistance in AGS by upregulating the expression of integrin β3, focal adhesion protein (FAK), and cofilin proteins. These results reveal that integrin β3, focal adhesion protein (FAK), and cofilin proteins are potential targets for the improvement of fluorouracil efficacy in gastric cancer treatment.

scholarly journals Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the β-Catenin/TCF/LEF-1 pathway in gastric cancer cells

2013 ◽  
Vol 42 (5) ◽  
pp. 2988-2998 ◽  
Author(s):  
Xiaoli Tang ◽  
Dong Zheng ◽  
Ping Hu ◽  
Zongyue Zeng ◽  
Ming Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cancer Tissue ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Cell Functions

Abstract Glycogen synthase kinase 3 beta (GSK3β) is a critical protein kinase that phosphorylates numerous proteins in cells and thereby impacts multiple pathways including the β-Catenin/TCF/LEF-1 pathway. MicroRNAs (miRs) are a class of noncoding small RNAs of ∼22 nucleotides in length. Both GSK3β and miR play myriad roles in cell functions including stem cell development, apoptosis, embryogenesis and tumorigenesis. Here we show that GSK3β inhibits the expression of miR-96, miR-182 and miR-183 through the β-Catenin/TCF/LEF-1 pathway. Knockout of GSK3β in mouse embryonic fibroblast cells increases expression of miR-96, miR-182 and miR-183, coinciding with increases in the protein level and nuclear translocation of β-Catenin. In addition, overexpression of β-Catenin enhances the expression of miR-96, miR-182 and miR-183 in human gastric cancer AGS cells. GSK3β protein levels are decreased in human gastric cancer tissue compared with surrounding normal gastric tissue, coinciding with increases of β-Catenin protein, miR-96, miR-182, miR-183 and primary miR-183-96-182 cluster (pri-miR-183). Furthermore, suppression of miR-183-96-182 cluster with miRCURY LNA miR inhibitors decreases the proliferation and migration of AGS cells. Knockdown of GSK3β with siRNA increases the proliferation of AGS cells. Mechanistically, we show that β-Catenin/TCF/LEF-1 binds to the promoter of miR-183-96-182 cluster gene and thereby activates the transcription of the cluster. In summary, our findings identify a novel role for GSK3β in the regulation of miR-183-96-182 biogenesis through β-Catenin/TCF/LEF-1 pathway in gastric cancer cells.

scholarly journals Inhibitory Effect of β-Carotene on Helicobacter pylori-Induced TRAF Expression and Hyper-Proliferation in Gastric Epithelial Cells

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 637 ◽  
Author(s):  
Yongchae Park ◽  
Hanbit Lee ◽  
Joo Weon Lim ◽  
Hyeyoung Kim
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Nadph Oxidase ◽  
Gastric Epithelial Cells ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
H Pylori ◽  
Β Carotene

Helicobacter pylori infection causes the hyper-proliferation of gastric epithelial cells that leads to the development of gastric cancer. Overexpression of tumor necrosis factor receptor associated factor (TRAF) is shown in gastric cancer cells. The dietary antioxidant β-carotene has been shown to counter hyper-proliferation in H. pylori-infected gastric epithelial cells. The present study was carried out to examine the β-carotene mechanism of action. We first showed that H. pylori infection decreases cellular IκBα levels while increasing cell viability, NADPH oxidase activity, reactive oxygen species production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, and TRAF1 and TRAF2 gene expression, as well as protein–protein interaction in gastric epithelial AGS cells. We then demonstrated that pretreatment of cells with β-carotene significantly attenuates these effects. Our findings support the proposal that β-carotene has anti-cancer activity by reducing NADPH oxidase-mediated production of ROS, NF-κB activation and NF-κB-regulated TRAF1 and TRAF2 gene expression, and hyper-proliferation in AGS cells. We suggest that the consumption of β-carotene-enriched foods could decrease the incidence of H. pylori-associated gastric disorders.

scholarly journals Effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of gastric cancer cells

2019 ◽  
Vol 17 ◽  
pp. 205873921984553
Author(s):  
Ying Guo ◽  
Li Zhang ◽  
Guangyu Zhou ◽  
Qingjie Ma ◽  
Shi Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Negative Control ◽  
Control Group ◽  
Gastric Cancer Cells ◽  
Ags Cells

This study was designed to investigate the effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of AGS gastric cancer cell. siRNA Bmi-1 was transfected into human AGS gastric cancer cells by liposome (as siRNA Bmi-1 group) with negative control (as control group); the expressions of Bmi-1 and apoptosis-related genes like P21, Bax, and Bcl-2 in AGS cells were determined by Western blot method; the apoptosis of AGS cells was detected by flow cytometry double staining and Hoechst staining; and cell cycle was measured by flow cytometry. Compared with the control group, the expression of Bmi-1 in the siRNA Bmi-1 group was significantly decreased ( P < 0.05), the apoptosis rate was increased ( P < 0.05), and cell cycles were arrested at G1 phase (P < 0.05); the expression level of P21 and Bax in cells was significantly up-regulated while that of Bcl-2 down-regulated ( P < 0.05). The down regulation of Bmi-1 can inhibit the proliferation of AGS gastric cancer cell and promote its apoptosis, which takes such effects mainly by up-regulating P21 as well as Bax and down-regulating Bcl-2.

scholarly journals The Complex Toxicity of Tetracycline with Polystyrene Spheres on Gastric Cancer Cells

2020 ◽  
Vol 17 (8) ◽  
pp. 2808 ◽  
Author(s):  
Xiemin Yan ◽  
Yuanyuan Zhang ◽  
Yuqin Lu ◽  
Lei He ◽  
Junhao Qu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Defense Mechanism ◽  
Natural Environments ◽  
Polystyrene Spheres ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Oxidation Stress ◽  
Strong Adsorption

Nowadays, microplastics (MPs) exist widely in the marine. The surface has strong adsorption capacity for antibiotics in natural environments, and the cytotoxicity of complex are poorly understood. In the study, 500 nm polystyrene (PS-MPs) and 60 nm nanoplastics (PS-NPs) were synthesized. The adsorption of PS to tetracycline (TC) was studied and their toxicity to gastric cancer cells (AGS) was researched. The adsorption experimental results show that PS absorbing capacity increased with increasing TC concentrations. The defense mechanism results show that 60 nm PS-NPs, 500 nm PS-MPs and their complex induce different damage to AGS cells. Furthermore, 600 mg/L PS-NPs and PS-MPs decline cell viability, induce oxidation stress and cause apoptosis. There is more serious damage of 60 nm PS-NPs than 500 nm PS-MPs in cell viability and intracellular reactive oxygen species (ROS). DNA are also damaged by 60 nm PS-NPs and PS-TC NPs, 500 nm PS-MPs and PS-TC MPs, and 60 nm PS-NPs damage DNA more serious than 500 nm PS-MPs. Moreover, 60 nm PS-NPs and PS-TC NPs seem to promote bcl-2 associated X protein (Bax) overexpression. All treatments provided us with evidence on how PS-NPs, PS-MPs and their compounds damaged AGS cells.

scholarly journals WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

2016 ◽  
Vol 39 (6) ◽  
pp. 2149-2157 ◽  
Author(s):  
Xiangshu Xian ◽  
Liuye Huang ◽  
Bo Zhang ◽  
Chengrong Wu ◽  
Jun Cui ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cannabis Sativa ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Active Components ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Mesenchymal Transition ◽  
Cox 2

Background: Cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis. Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN) was associated with gastric cancer (GC) metastasis, but the mechanisms were unknown. Methods: The effects of WIN on GC cell migration and invasion were analyzed by the wound-healing assay and Transwell assay. Quantitative real-time PCR and Western blot were used to evaluate changes in expression of COX-2 and EMT associated markers in SGC7901 and AGS cells. Results: WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT) in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2) expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells. Conclusion: WIN can inhibit the EMT of GC cells through the downregulation of COX-2.

scholarly journals Investigating the Effects of Salvia chorassanica Bunge and Shoot Extracts on Gastric Cancer Cells: Evidence of Different Behavior on Various Tumor Grades

2020 ◽  
Vol 27 (3) ◽  
pp. 378-384
Author(s):  
Fatemeh Karami ◽  
Ahmad Dourandish Yazdi ◽  
Iman Salahshourifar ◽  
Mohsen Marvi Beigi
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Leaf Extract ◽  
P Value ◽  
Root Extract ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Expression Ratio ◽  
Anticancer Effects

Background: Different Salvia species have demonstrated anti-proliferative effects on various cancer cells. Owing to the poor literature on the anti-proliferative effects of Salvia species on gastric cancer cells, present study was conducted to determine the anticancer effects of a local Iranian Salvia, Salvia chorassanica, on two different gastric cell lines. Methods: Root, stem and leaf extract of Salvia chorassanica were prepared through maceration method and were then used to treat the AGS and MKN-45 cell lines in different concentrations. MTT assay was employed to determine the toxicity of all the types of extracts on the two studied cell lines. The expression of Bax, Bcl-2, Caspase3, MMP2 and MMP9 genes were determined through reverse transcription Real time PCR (RT-PCR). Results: Bunge and shoot extracts demonstrated toxicity in both cell lines which were more considerable in AGS cells treated with root extract. In contrary to AGS cells, Caspase3 gene was up-regulated in all types of treatment while the MMP2 and MMP9 genes were down-regulated (p-value<0.001). Except of the MKN-45 cells treated with leaf extract, Bax/Bcl-2 expression ratio was decreased in the treatment with all types of Salvia chorassanica extracts (p-value<0.001). Conclusion: Remarkable low IC50 concentration of root extract in MKN-45 cell line is indicating the significant cytotoxicity of Salvia chorassanica against gastric cancer cells. Moreover, gene expression analysis in MKN-45 needs further confirmation on the potential anti-metastatic roles of leaf and root extracts in higher grades of gastric cancer.

scholarly journals MiR-496 Inhibits the Proliferation Through Targeting LYN and AKT/mTOR Signaling Pathway in Gastric Cancer

2020 ◽  
Author(s):  
Rui Su ◽  
Enhong Zhao ◽  
Jun Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Mtor Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Ags Cells

Abstract MiRNA operates as a tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis and metabolic process. In the present research, we investigated the effect and mechanism of miR496 in human gastric cancer cells. Cell proliferation was measured by CCK8 and clonogenic assay. Transwell test was performed to detect cell migration and invasion. Flow cytometry analysis was used to evaluate cell apoptosis. Bioinformatics software targetscan was used for the screening of miR-496’s target gene. MiR-496 was down regulated in three gastric cancer cell lines, SGC-790, AGS and MKN45 compared with normal gastric epithelial cell line GES-1. MiR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 h and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. In addition, miR-496 mimics induced the apoptosis through up regulating the levels of Bax and Active Caspase3 and down regulating the levels of Bcl-2 and Total Caspase3. Bioinformatics analysis showed that there was a binding site between miR-496 and LYN kinase (LYN). MiR-496 mimics could inhibit the expression of LYN in AGS cells. The overexpression of LYN blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496 in gastric cancer cells. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment of gastric cancer.

scholarly journals Chrysophanol Inhibits the Progression of Gastric Cancer by Activating NLRP3

2021 ◽  
Author(s):  
Hou Binfen ◽  
Li Zhao ◽  
Min Deng
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Antitumor Effects ◽  
Ags Cells ◽  
Anti Cancer ◽  
Colony Forming Assay

Abstract AimGastric cancer is one of the most common malignant tumors.Chrysophanol has been reported to have antitumor effects on a variety of cancers, but the role of chrysophanol in gastric cancer remains unclear. The aim of this study was to investigate the effects of chrysophanol on proliferation, pyroptosis, migration and invasion of gastric cancer cells.MethodsMKN 28 and AGS cells were treatde with different concentrations of chrysophanol, then cell proliferation, migration,invasion and pyroptosis were decteed by CCK-8, Colony-forming assay, Wound Healing assay, Transwell and flow cytometry, respectively.Subsequently, NLRP3 siRNA was transfected into MKN 28 cells, cell proliferation pyroptosis, migration and invasion were reassessed in these transfected cells. The expression of caspase-1 and IL-1β in the downstream of NLRP3 was detected by qRT PCR and Western blot.ResultsChrysophanol significantly inhibited the proliferation of GC cells, promoted pyroptosis, inhibited cell migration and invasion, and up-regulated the expression level of NLRP3 inflammasome in GC cells. Silencing NLRP3 inhibited the effects of chrysophanol on proliferation, pyroptosis, migration and invasion of MKN 28 cells. Chrysophanol plays an anti-cancer role through high expression of NLRP3.CoclusionsChrysophanol can inhibit the proliferation, migration and invasion of gastric cancer cells by regulating NLRP3, promote the death of gastric cancer cells, and play an anti-tumor role,which is a clinical strategy with great potential for the treatment of gastric cancer.

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