scholarly journals Betulinic Acid, a Pentacyclic Triterpene, Inhibits Prosurvival Endoplasmic Reticulum Chaperone GRP78/BIP Expression and Induces Mitochondrial‐Dependent Apoptosis in Gastric Cancer Cells

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Ming‐wei Lin ◽  
Chia‐Yuan Hsieh ◽  
Fang‐rong Chang ◽  
Deng‐chyang Wu ◽  
Chun‐lin Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endoplasmic Reticulum ◽  
Cancer Cells ◽  
Betulinic Acid ◽  
Gastric Cancer Cells ◽  
Pentacyclic Triterpene ◽  
Endoplasmic Reticulum Chaperone

scholarly journals Mevalonate Pathway Enzyme HMGCS1 Contributes to Gastric Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1088 ◽  
Author(s):  
I-Han Wang ◽  
Tzu-Ting Huang ◽  
Ji-Lin Chen ◽  
Li-Wei Chu ◽  
Yueh-Hsin Ping ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endoplasmic Reticulum ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Nuclear Translocation ◽  
Mevalonate Pathway ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Progression

The 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) is a potential regulatory node in the mevalonate pathway that is frequently dysregulated in tumors. This study found that HMGCS1 expression is upregulated in stomach adenocarcinoma samples of patients and tumorspheres of gastric cancer cells. HMGCS1 elevates the expression levels of the pluripotency genes Oct4 and SOX-2 and contributes to tumorsphere formation ability in gastric cancer cells. HMGCS1 also promotes in vitro cell growth and progression and the in vivo tumor growth and lung metastasis of gastric cancer cells. After blocking the mevalonate pathway by statin and dipyridamole, HMGCS1 exerts nonmetabolic functions in enhancing gastric cancer progression. Furthermore, the level and nuclear translocation of HMGCS1 in gastric cancer cells are induced by serum deprivation. HMGCS1 binds to and activates Oct4 and SOX-2 promoters. HMGCS1 also enhances the integrated stress response (ISR) and interacts with the endoplasmic reticulum (ER) stress transducer protein kinase RNA-like endoplasmic reticulum kinase (PERK). Our results reveal that HMGCS1 contributes to gastric cancer progression in both metabolic and nonmetabolic manners.

scholarly journals Casticin Potentiates TRAIL-Induced Apoptosis of Gastric Cancer Cells through Endoplasmic Reticulum Stress

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e58855 ◽  
Author(s):  
Yuan Zhou ◽  
Li Tian ◽  
Lingzhi Long ◽  
Meifang Quan ◽  
Fei Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Gastric Cancer Cells ◽  
Induced Apoptosis

OSU-03012 induces apoptosis of gastric cancer cells through endoplasmic reticulum stress triggered inhibition of Akt and STAT3 signaling pathways.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15630-e15630
Author(s):  
Wei Peng ◽  
Xia Xu ◽  
Xiaoxiang Chen ◽  
Jifeng Feng ◽  
Bo Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Preclinical Development ◽  
Gastric Cancer Cells ◽  
Stat3 Signaling ◽  
Caspase Family

e15630 Background: As the chemotherapeutic resistance and postoperative relapse rates of gastric cancer rise year by year, searching for novel chemoprevention compounds has become fairly imminent. 2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide (OSU-03012), a derivative of anti-inflammatory drug celecoxib, has recently been shown to have anti-tumor effects. But its roles and underling mechanisms in gastric cancer is rather unknown. Methods: In this study, we show for the first time that OSU-03012 inhibits the growth and potently induces the apoptosis of gastric cancer cells in vitro in a time- and dose-dependent manner. Results: We demonstrate that OSU-03012 induces cell death through endoplasmic reticulum stress (ERS) mediated up-regulation of PTEN, sequentially followed by the suppression of Akt-STAT3 axis, the activation of the mitochondrial membrane protein Bim, mitochondrial damage and finally the release of the caspase family proteases. Conclusions: Our data provide evidences to support OSU-03012 as a potential therapeutic agent for gastric cancer, which may facilitate further preclinical development of anti-tumor drugs.

Effect of proton pump inhibitors on the occurrence and development of gastric cancer and the polarization of macrophages in the microenvironment to M2-type.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 437-437
Author(s):  
Xiao-Qing Lu ◽  
Shengxiao Zhang ◽  
Huan-Hu Zhang
Keyword(s):  
Gastric Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Signal Pathways ◽  
Main Role ◽  
Gastric Cancer Cells ◽  
Cancer Tissues

437 Background: Long-term use of Proton pump inhibitors was associated with an increased gastric cancer(GC) risk in subjects even after HP eradication therapy. In contrast some basic research showed that PPI inhibited the growth of GC. In the tumor-microenvironment (TME), macrophages that are recruited around the tumor are activated to form the tumor-associated macrophages (TAMs), which are the most abundant mononuclear cells in the tumor infiltrating leukocytes. Many studies have shown that TAMs are associated with poor prognosis of tumors. Methods: Immunohistochemistry was used to detect the phenotype of macrophages in patients with gastric cancer treated with PPI or without PPI. Transcriptomics sequencing analyzed the signal pathways that were highly expressed in PPI-treated gastric cancer for further exploring the mechanism of PPI's main role in gastric cancer cells. In vitro, explore the effects of PPI on gastric cancer cells and the next step on macrophages. The effects of PPI on the growth of gastric cancer and the degree of infiltration and phenotype transformation of macrophages were verified by in vivo experiments. Results: In the gastric cancer tissues treated with PPI, the macrophage phenotype is mostly M2 type, thereby exerting a cancer promoting effects. Transcriptome results showed high expression of genes associated with endoplasmic reticulum stress in gastric cancer tissues after PPI treatment, compared with patients who were not treated with PPI. Among them, GRP78 is a classic marker of endoplasmic reticulum stress. It was not only highly expressed in gastric cancer treated by PPI, but also acted on macrophages through exosomes secreted by gastric cancer cells, and caused macrophage to polarize to M2. Conclusions: PPI caused GC cells to overexpress GRP78 which was secrete into the microenvironment through exosomes, thereby transforming macrophages into M2 type under the action of GRP78. Finally M2 type macrophages promoted the progression of gastric cancer.

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