scholarly journals MS-Based Metabolomics Reveals Metabolic Dysregulation in Erastin-Induced Gastric Adenocarcinoma Cells

2021 ◽  
Author(s):  
Ying Liu ◽  
Wenchao Hu ◽  
Mogesdessale Asmamaw ◽  
Lulu Pan ◽  
Juan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cellular Response ◽  
Ion Trap ◽  
Malignant Tumors ◽  
Tca Cycle ◽  
Drug Candidate ◽  
High Morbidity ◽  
Gastric Cancer Cells ◽  
Gastric Cells

Abstract Gastric cancer (GC) is one of the most malignant tumors with high morbidity and mortality in the world, particularly in China. Erastin, a classical ferroptosis inducer, exerts cytotoxicity in several types of cancer cells including gastric cancer cells. However, the mechanism of erastin in regulating metabolic pathways in gastric cancer remains largely unclear. To investigate the gastric cellular response to erastin therapy, we adopted a cell pseudotargeted metabolomics method based on liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (LC-QTRAP MS). The developed method was used to investigate the differential metabolites between erastin-treated MGC-803 cells and the controls at different time points. We found that erastin induced tremendous impact on the metabolome of gastric cells by affecting key metabolic processes, such as cysteine and methionine metabolism, glutathione (GSH) biosynthesis, glycolysis and TCA cycle. Interestingly, S-adenosylmethionine (SAM), methionine, serine, glycine and cysteine were obviously increasing treads after erastin treatment, but S-adenosylhomocysteine (SAH) and GSH were always down-regulated up to 48 h. The results indicated that DNA methylation was activated and glutathione biosynthesis was blocked in erastin-treated MGC-803 gastric cells, highlighting the importance of erastin as a promising drug candidate for in vivo treatment of gastric tumor.

scholarly journals CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ling Gao ◽  
Tingting Xia ◽  
Mingde Qin ◽  
Xiaofeng Xue ◽  
Linhua Jiang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
High Morbidity ◽  
Gastric Cancer Cells ◽  
Mirna Sponges ◽  
Gastric Cancer Cell Proliferation

BackgroundGastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown.MethodsCircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK).ResultsThe level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer.ConclusionCollectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.

scholarly journals Potent and specific MTH1 inhibitors targeting gastric cancer

2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Wenjuan Zhou ◽  
Liying Ma ◽  
Jing Yang ◽  
Hui Qiao ◽  
Lingyu Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Malignant Tumors ◽  
Inhibitory Effect ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Dntp Pool ◽  
Cancer Tissues

Abstract Human mutT homolog 1(MTH1), the oxidized dNTP pool sanitizer enzyme, has been reported to be highly expressed in various malignant tumors. However, the oncogenic role of MTH1 in gastric cancer remains to be determined. In the current study, we found that MTH1 was overexpressed in human gastric cancer tissues and cells. Using an in vitro MTH1 inhibitor screening system, the compounds available in our laboratory were screened and the small molecules containing 5-cyano-6-phenylpyrimidine structure were firstly found to show potently and specifically inhibitory effect on MTH1, especially compound MI-743 with IC50 = 91.44 ± 1.45 nM. Both molecular docking and target engagement experiments proved that MI-743 can directly bind to MTH1. Moreover, MI-743 could not only inhibit cell proliferation in up to 16 cancer cell lines, especially gastric cancer cells HGC-27 and MGC-803, but also significantly induce MTH1-related 8-oxo-dG accumulation and DNA damage. Furthermore, the growth of xenograft tumours derived by injection of MGC-803 cells in nude mice was also significantly inhibited by MI-743 treatment. Importantly, MTH1 knockdown by siRNA in those two gastric cancer cells exhibited the similar findings. Our findings indicate that MTH1 is highly expressed in human gastric cancer tissues and cell lines. Small molecule MI-743 with 5-cyano-6-phenylpyrimidine structure may serve as a novel lead compound targeting the overexpressed MTH1 for gastric cancer treatment.

scholarly journals Luteolin Suppresses the Proliferation of Gastric Cancer Cells and Acts in Synergy with Oxaliplatin

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Li-Qun Ren ◽  
Qi Li ◽  
Yang Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Gastric Cancer Cells ◽  
Antitumor Effects ◽  
Cyt C ◽  
Induced Apoptosis ◽  
Vegetables And Fruits

Objective. Gastric cancer, one of the most common malignant tumors worldwide, arises from the gastric mucosal epithelium and severely affects patient health and quality of life. Luteolin (LUT) is a flavonoid found in vegetables and fruits with diverse functions. A large number of studies have confirmed that LUT has an antitumor effect. Therefore, this study is aimed at verifying whether LUT can exert antitumor effects in synergy with oxaliplatin (OXA). As such, we examined the effects of LUT, OXA, and their coadministration in a gastric adenocarcinoma cell line (SGC-7901). We used the MTT assay to quantify the proliferation of SGC-7901 cells, flow cytometry to detect the cell cycle and apoptosis, ELISA to detect the expression of cell-cycle-related proteins, and western blot to detect the expression of related apoptotic factors. The results of this study show that the combination of LUT and OXA inhibited SGC-7901 cell proliferation and induced apoptosis by altering cell-cycle proportions. In addition, the combination also activated Cyt c/caspase signaling in SGC-7901 cells. In summary, LUT synergy with OXA inhibited the proliferation of gastric cancer cells in vitro. The present study also elucidated the mechanism by which LUT potentiated the sensitivity of SGC-7901 cells to OXA through the Cyt c/caspase pathway.

scholarly journals Gramicidin inhibits human gastric cancer cell proliferation, cell cycle and induced apoptosis

2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Tingting Chen ◽  
Yong Wang ◽  
Yang Yang ◽  
Kaikai Yu ◽  
Xiangliao Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
High Morbidity ◽  
Peptide Antibiotic ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Gastric Mucosal Cells ◽  
Mucosal Cells

Abstract Background Gastric cancer is a common malignant tumor with high morbidity and mortality worldwide, which seriously affects human health. Gramicidin is a short peptide antibiotic which could be used for treating infection induced by bacteria or fungi. However, the anti-cancer effect of gramicidin on gastric cancer cells and its underlying mechanism remains largely unknown. Results Gastric cancer cells SGC-7901, BGC-823 and normal gastric mucosal cells GES-1 were treated with different concentrations of gramicidin respectively. The results of CCK-8 experiment revealed cellular toxicity of gramicidin to cancer cells while cell colony formation assay showed that gramicidin significantly inhibited the proliferation of gastric cancer cells, but had little effect on normal gastric mucosal cells. In addition, the wound healing assay showed that gramicidin inhibited the migration of SGC-7901 cell. Meanwhile, apoptosis and cell cycle analysis revealed that gramicidin induced cell apoptosis with G2/M cell cycle inhibition. Furthermore, western blot analysis demonstrated that gramicidin down-regulated the expression of cyclinD1 and Bcl-2 as well as the FoxO1 phosphorylation. Conclusions The current study illustrated the anti-tumor activity of gramicidin on gastric cancer cells, providing a possibility for gramicidin to be applied in clinical practice for the treatment of gastric cancer.

miR-375 targets the p53 gene to regulate cellular response to ionizing radiation and etoposide in gastric cancer cells

DNA Repair ◽  
2013 ◽  
Vol 12 (9) ◽  
pp. 741-750 ◽  
Author(s):  
Yixuan Liu ◽  
Rui Xing ◽  
Xiaodong Zhang ◽  
Weiwei Dong ◽  
Jingyu Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Ionizing Radiation ◽  
Cancer Cells ◽  
Cellular Response ◽  
P53 Gene ◽  
Gastric Cancer Cells

scholarly journals GTPBP4 Promotes Gastric Cancer Progression via Regulating P53 Activity

2018 ◽  
Vol 45 (2) ◽  
pp. 667-676 ◽  
Author(s):  
Li Li ◽  
Xunlei Pang ◽  
Zuan Zhu ◽  
Lili Lu ◽  
Jun Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
High Throughput Sequencing ◽  
Health Concern ◽  
High Morbidity ◽  
Gastric Epithelial Cells ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

Background/Aims: gastric cancer is a serious health concern with high morbidity and mortality. Therefore, it is urgent to find novel targets for gastric cancer diagnosis and treatment. Methods: qRT-PCR and immunohistochemistry assays were used to detect GTPBP4 expression in gastric cancer tissues, and gastric cancer and gastric epithelial cells. Lentivirus infection was used to construct GTPBP4 stable knockdown cells. Annexin V/PI apoptosis, CCK8, EdU incorporation and cell clone formation analysis were performed to evaluate the effects of GTPBP4 on gastric cancer cell proliferation and apoptosis. Further RNA-based high-throughput sequencing and co-IP assays were constructed to explore the related mechanisms contributing to GTPBP4-mediated effects. Results: GTPBP4 expression was significantly increased in gastric cancer tissues compared with that in adjacent normal tissues, and positively correlated with gastric cancer stages. Meanwhile, GTPBP4 level was markedly upregulated in gastric cancer cells than in gastric epithelial cells. Additionaly, stable knockdown of GTPBP4 inhibited cell proliferation and promoted cell apoptosis. Mechanistically, p53 and its related signaling were significantly activated in GTPBP4 stable knockdown cells. And GTPBP4 interacted with p53 in gastric cancer cells. Conclusions: our results provide insights into mechanistic regulation and linkage of the GTPBP4-p53 in gastric cancer, and also a valuable potential target for gastric cancer.

Inhibition of autophagy improves resistance and enhances sensitivity of gastric cancer cells to cisplatin

2020 ◽  
Vol 98 (7) ◽  
pp. 449-458 ◽  
Author(s):  
Guiqin Hou ◽  
Yiru Bai ◽  
Ang Jia ◽  
Yandan Ren ◽  
Yang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Beclin 1 ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Concentration Dependent Manner ◽  
Gastric Cells ◽  
Enhanced Sensitivity ◽  
Mtorc1 Pathway ◽  
Autophagy Activity

Autophagy plays critical roles in tumorigenesis, while the effects of autophagy on chemoresistance of cancer cells had great disparity. This study aims to explore the impacts of autophagy on the sensitivity and resistance of gastric cancer cells to cisplatin (DDP). We firstly demonstrated that there was stronger autophagy activity in gastric cancer SGC-7901 cells than that in DDP-resisting SGC-7901/DDP cells. Then, we discovered that inhibiting autophagy by chloroquine (CQ) significantly enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP to SGC-7901 and SGC-7901/DDP cells. Moreover, CQ could partially reverse the resistance of SGC-7901/DDP cells to DDP in a concentration-dependent manner. However, the autophagy inducer everolimus (RAD001) had no obvious effects on the sensitivity of gastric cells to DDP. Mechanistically, we demonstrated that CQ might enhance the sensitivity of SGC-7901cells and improve the resistance of SGC-7901/DDP cells to DDP through inhibiting the mTORC1 pathway, especially to SGC-7901/DDP cells. Additionally, we found interfering Beclin-1 using Beclin-1 shRNA also enhanced the proliferation-inhibiting and apoptosis-inducing effects of DDP on gastric cancer cells by inhibiting phosphorylation of Akt. Our study shows that inhibiting autophagy could improve the chemoresistance and enhanced sensitivity of gastric cancer cells to DDP and provide a rationale for the administration of cisplatin combined with CQ for treating patients with gastric cancer.

scholarly journals Quinolinone inhibits proliferation of gastric cancer cells and induces their apoptosis via down-regulation of the expression of pro-oncogene c-Myc

2020 ◽  
Vol 19 (8) ◽  
pp. 1599-1604
Author(s):  
Jing Ma ◽  
Xinrui Chen ◽  
Baoli Xu ◽  
Wenguang Liu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Underlying Mechanism ◽  
Drug Candidate ◽  
Proliferative Potential ◽  
Gastric Cancer Cells ◽  
Expression Levels ◽  
Invasion And Migration ◽  
Keywords Gastric Cancer ◽  
And Migration

Purpose: To determine the anti-proliferative potential of quinolinone against gastric cancer cells, and the underlying mechanism of action.Methods: Quinolinone-mediated proliferative changes were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while its effect on apoptosis was determined by flow cytometry. Transwell and wound healing assays were used for the determination of the effect of quinolinone on cell invasion and migration. The effect of quinolinone on protein expression levels were assayed with western blotting.Results: Quinolinone caused reduction in gastric cancer cell viability, but it had no effect on normal (GES-1) cells. Treatment with 8 μM quinolinone reduced the viability of SNU-5 and SGC-7901 cells to 32 and 27 %, respectively. Moreover, 8 μM quinolinone induced 67.90 and 71.54 % apoptosis in SNU-5 and SGC-7901 cells, respectively. Quinolinone significantly increased the population of cells in G1 phase, and suppressed migration potential (p < 0.05). Furthermore, in quinolinone-treated cells, the expression levels of p-PI3K, c-Myc and p-AKT were much lower than those in untreated cells (p < 0.05). Quinolinone also downregulated the expressions of MMP-2 and MMP-9, while it upregulated p21 expression in SNU-5 and SGC-7901 cells.Conclusion: Quinolinone suppresses the growth of SNU-5 and SGC-7901 gastric cancer cells via cell cycle arrest, induction of apoptosis and downregulation of the expressions of c-Myc and metalloproteinases. Thus, quinolinone may be developed as a potential drug candidate for the treatment of gastric cancer. Keywords: Gastric cancer, Apoptosis, Metalloproteinases, Phosphorylation

scholarly journals Bruceine D inhibits Cell Proliferation Through Downregulating LINC01667/MicroRNA-138-5p/Cyclin E1 Axis in Gastric Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Lin Li ◽  
Zhen Dong ◽  
Pengfei Shi ◽  
Li Tan ◽  
Jie Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Gastric Cancer Cells ◽  
Western Blot Assay ◽  
Cyclin E1

Objective: Gastric cancer is one of the most common malignant tumors. Bruceine D (BD) is one of the extracts of Brucea javanica. In recent years, it has been reported that BD has anti-tumor activity in some human cancers through different mechanisms. Here, this study try to explore the effect of BD on gastric cancer and its regulatory mechanism.Methods: Cell proliferation ability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, 5-bromo-2-deoxyuridine (BrdU) staining and soft agar colony formation assay, respectively. The tumor xenograft model was used to verify the effect of BD on the tumorigenicity of gastric cancer cells in vivo. Flow cytometry analysis and Western blot assay were performed to detect cell cycle and apoptosis. Gastric cancer cells were analyzed by transcriptome sequencing. The interaction between LINC01667, microRNA-138-5p (miR-138-5p) and Cyclin E1 was verified by dual luciferase experiment and RT-PCR assays.Results: We found that BD significantly inhibited cell proliferation and induced cell cycle arrest at S phase in gastric cancer cells. Transcriptome analysis found that the expression of a long non-coding RNA, LINC01667, were significantly down-regulated after BD treatment. Mechanically, it was discovered that LINC01667 upregulated the expression of Cyclin E1 by sponging miR-138-5p. Furthermore, BD enhanced the chemosensitivity of gastric cancer cells to doxorubicin, a clinically used anti-cancer agent.Conclusion: BD inhibit the growth of gastric cancer cells by downregulating the LINC01667/miR-138-5p/Cyclin E1 axis. In addition, BD enhances the chemosensitivity of gastric cancer cells to doxorubicin. This study indicates that BD may be used as a candidate drug for the treatment of patients with gastric cancer.

scholarly journals LOW CONCENTRATION OF BISPHENOL A INDUCES PROLIFERATION OF GASTRIC CANCER CELLS, HGC-27

2019 ◽  
Vol 81 (6) ◽  
Author(s):  
Noorul Izzati Hanafi ◽  
Siti Hamimah Sheikh Abdul Kadir ◽  
Maslinda Musa ◽  
Mohd Hafiz Dzarfan Othman ◽  
Roziana Kamaludin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bisphenol A ◽  
Cell Viability ◽  
Cancer Cells ◽  
Endocrine Disrupting Compounds ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Low Concentration ◽  
Gastric Cells ◽  
The Impact

Bisphenol A, an endocrine disrupting compounds that affect human homeostasis. Studies on BPA are focusing on the impact of BPA in reproductive function and brain development. However, the effect of BPA on gut especially gastric cells is not well explored. Gut is directly in contact with ingested BPA; therefore, we aimed to determine the effect of BPA exposure on gastric cells proliferation at safe recommended concentration. Human gastric cancer cells (HGC-27) were treated with BPA at different concentration (low: 10-9M, 10-7M; high10-5M, 10-4M) and time point (24 hr, 48 hr, 72 hr). Cell viability assays were determined using MTS assay. Cells were further stained with Alexa Fluor-635 (F-actin) and Fluorescein (Hif-1α) protein for immunocytofluorescence. Data were analysed using ANOVA (p<0.05, n≥3). Cells treated with 10-9M BPA showed significance increase of cell viability after 48 hr (Mean ±SEM; 146%±0.03, p=0.01) and 72 hr (113%±0.03, p=0.00) compared to 24 hr treatment (77%±0.11, p=0.002). Similarly, cell treated with 10-7M BPA showed a significance increase after 48 hr (141%±0.03, p=0.03) and 72 hr (190%±0.03, p=0.02) compared to 24 hr cells treated with 10-7M (88%±0.05, p=0.01) and untreated (100%±0.07). Lower concentration of BPA increases the condensation of F-actin in all HGC-27 cells. Meanwhile, translocation of Hif-1α protein were observed in all BPA-exposed cells. Findings of this study revealed that BPA induced proliferation and condensation of F-actin structure of gastric cancer cells at low concentration.

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