• Molecules and Cells
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• v.39 no.10
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• pp.742-749
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• 2016

The cancer chemo-preventive effects of equol have been demonstrated for a wide variety of experimental tumours. In a previous study, we found that equol inhibited proliferation and induced apoptotic death of human gastric cancer MGC-803 cells. However, the mechanisms underlying equol-mediated apoptosis have not been well understood. In the present study, the dual AO (acridine orange)/EB (ethidium bromide) fluorescent assay, the comet assay, MTS, western blotting and flow cytometric assays were performed to further investigate the pro-apoptotic effect of equol and its associated mechanisms in MGC-803 cells. The results demonstrated that equol induced an apoptotic nuclear morphology revealed by AO/EB staining, the presence of a comet tail, the cleavage of caspase-3 and PARP and the depletion of cIAP1, indicating its pro-apoptotic effect. In addition, equol-induced apoptosis involves the mitochondria-dependent cell-death pathway, evidenced by the depolarization of the mitochondrial membrane potential, the cleavage of caspase-9 and the depletion of Bcl-xL and full-length Bid. Moreover, treating MGC-803 cells with equol induced the sustained activation of extracellular signal-regulated kinase (ERK), and inhibiting ERK by U0126, a MEK/ERK pathway inhibitor, significantly attenuated the equol-induced cell apoptosis. These results suggest that equol induces mitochondria-dependent apoptosis in human gastric cancer MGC-803 cells via the sustained activation of the ERK1/2 pathway. Therefore, equol may be a novel candidate for the chemoprevention and therapy of gastric cancer.

• Applied Microscopy
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• v.39 no.3
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• pp.205-218
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• 2009

This experiment was performed to evaluate the morphological responses of the gastric epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of BCG. Healthy adult ICR mice weighing 25 gm each were divided into normal and experimental groups (tumor control group and BCG-treated group). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8{\sim}0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of 0.7 ${\mu}Ci/g$ of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab., England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and gastric tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab., England) in a dark room. The number of labeled epithelial cells in the gastric mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. And for electron microscopic observation, gastric tissues were prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde solution, followed by post-fixation with 1% osmium tetroxide solution. On the light microscopic study, gastric mucosae had no morphological changes following the injection of BCG. On the electron microscopic study, in the BCG-treated mice, myelin figures and multivesicular bodies within the gastric epithelial cells were observed more frequently than in those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 380.2 (${\pm}31.35$), 426.1 (${\pm}28.43$) and 301.8 (${\pm}34.63$), respectively. In the BCG-treated mice, poorly-labeled cells containing only a few silver grains of 3H-thymidine were observed more frequently as compared in those of the normal control and tumor control ones. From the above results, BCG may suppress the DNA synthesis of the gastric epithelial cells, but does not results severe fine structural defect on the gastric epithelial cells. These results suggest that BCG is expected as one of the effective supplemental anticancer drugs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.835-840
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• 2013

Accumulating evidence has shown that microRNAs are involved in cancer development and progression. However, it remains unknown about the potential role of miR-19a in the pathogenesis of gastric cancer. Here, we report that suppressor of cytokine signaling 1 (SOCS1) is a novel target of miR-19a in gastric cancer cells and that miR-19a expression is inversely correlated with SOCS1 expression in gastric cancer cells and a subset of gastric cancer tissues. Ectopic expression of miR-19a dramatically promoted proliferation and tumorigenicity of gastric cancer cells both in vitro and in vivo. Moreover, we showed that silencing of SOCS1 promoted cell growth and colony formation resembling that of miR-19a overexpression, whereas re-introduction of SOCS1 (without the 3'-UTR) attenuated the pro-tumorigenic functions. Taken together, our findings suggest that the SOCS1 gene is a direct target of miR-19a, which functions as an oncogenic miRNA in gastric cancer by repressing the expression of tumor suppressor SOCS1.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.326-337
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• 2003

In order to evaluate the prevention effect of Sunkiwhajung-tang (SWT) which has been used as a traditional prescription for the treatment of digestive disease in Korea on the gastric ulcer induced by indomethacin in rats, the changes of number and size of ulcerative lesions, parietal, chief, Grimelius and Serotonin-positive cells in the peri-ulcerative tissues were detected with histological examinations of ulcerative and peri-ulcerative lesions after oral injections of SWT extracts (125, 250 and 500 mg/kg, respectively). SWT prevented to a great extent the expected indomethacin-induced elevation in hemorrhagic ulcerative lesions, the number and size of ulcerative lesions, and the number of parietal cell, chief cell, Grimelius-positive cells and Serotonin-positive cells in the peri-ulcerative lesions in a dose dependent manner. These results provide a story evidence that SWT produced an protective effect on gastric ulcer induced by indomethacin. Determination of the specific mechanisms involved in the protective effect of SWT on the gastric ulcer will require additional study.

• Journal of Gastric Cancer
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• v.11 no.1
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• pp.59-63
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• 2011

Borrmann type 4 gastric cancers are notorious for the difficulty of finding cancer cells in the biopsy samples obtained from gastrofiberscopy. It is important to obtain the biopsy results for making surgical decisions. In cases with Borrmann type 4 gastric cancer, even though the radiological findings (such as an upper gastrointestinal series, abdominal computed tomography and positron emission tomography/computed tomography) or the macroscopic findings of a gastrofiberscopy examination imply a high suspicion of cancer, there can be difficulty in getting the definite pathologic results despite multiple biopsies. In these cases, we have performed endoscopic mucosal resection under gastrofiberscopy as an alternative to simple biopsies. Here we report on a case in which no cancer cells were found even in the endoscopic mucosal resection specimen, but the radiologic evidence and clinical findings were highly suspicious for gastric cancer. The patient finally underwent total gastrectomy with lymph node resection, and she was pathologically diagnosed as having stage IV gastric cancer postoperatively.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6305-6310
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• 2012

Objectives: This study aimed to demonstrate the tyrosine phosphorylation motif (TPM) and 3' region structure of the Helicobacter pylori CagA gene as well as its SHP-2 binding activity in AGS cells and relation to gastric carcinogenesis. Methods: Sixteen clinical isolate H. pylori strains from eight duodenal ulcer and eight gastric adenocarcinoma patients were studied for CagA repeat sequence EPIYA motifs, C-terminal structure, and western blot analysis of CagA protein expression, translocation, and SHP-2 binding in AGS cells. Results: Except for strain 547, all strains from the gastric adenocarcinoma patients were positive for CagA by PCR and had three EPIYA copy motifs. Western blotting showed that all strains were positive for CagA protein expression (100%), CagA protein translocation (100%), and SHP-2 binding (100%). CagA protein expression was significantly higher in the gastric adenocarcinoma patients than in the duodenal ulcer patients (P=0.0023). CagA protein translocation and SHP-2 binding in the gastric adenocarcinoma patients were higher than those in the duodenal ulcer patients, but no significant differences were found between the two groups (P=0.59, P=0.21, respectively). Conclusions: The TPMs and 3' region structures of the H. pylori CagA gene in the duodenal ulcer and gastric adenocarcinoma patients have no significant differences.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.487-492
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• 2011

In our previous study, we investigated Chenopodium album Linne (CAL) ethanol extract and its fractions on anti-gastritic actions using the HCl/ethanol and indomethacin induced gastric lesion model and Helicobacter pylori (H. pylori). Based on the results, butanol fraction was most effective among fractions obtained from CAL. This study aims to elucidate the mechanisms of butanol fraction, and betaine as a constituent of the butanol fraction, on gastritis and anti-gastric cancer cell growth. First, we examined antioxidant properties using hydrogen peroxide and superoxide radical, and we found that butanol fraction and betaine may be good antioxidants. Second, cytotoxicity was assessed by measuring cell viability and 4,6-diamidino-2-phenylinodole dihydrochloride (DAPI) staining of human gastric cancer cells (AGS cells). We also examined the relationship between the cytotoxicity and intracellular $Ca^{2+}$ signaling mechanism. The butanol fraction demonstrated cell viability 71.49% at the concentration of 100 ${\mu}g/ml$ and increased intracellular $Ca^{2+}$ concentration in a dose dependent manner. Finally, we observed the mucus content as a defensive factor and gastric secretion as an aggressive factor, and found that the mucus content noticeably increased when treated with butanol fraction and betaine and gastric secretion decreased when treated with betaine in vivo study. From these results, we suggest that CAL butanol fraction and betaine may have protective effects on gastritis.

• BMB Reports
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• v.56 no.8
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• pp.451-456
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• 2023

Deubiquitinases (DUBs) are an essential component of the ubiquitin-proteasome system (UPS). They trim ubiquitin from substrate proteins, thereby preventing them from degradation, and modulate different cellular processes. Ubiquitin-specific protease 14 (USP14) is a DUB that has mainly been studied for its role in tumorigenesis in several cancers. In the present study, we found that the protein levels of USP14 were remarkably higher in gastric cancer tissues than in the adjacent normal tissues. We also demonstrated that the inhibition of USP14 activity using IU1 (an USP14 inhibitor) or the inhibition of USP14 expression using USP14-specific siRNA markedly reduced the viability of gastric cancer cells and suppressed their migratory and invasive abilities. The reduction in gastric cancer cell proliferation due to the inhibition of USP14 activity was a result of the increase in the degree of apoptosis, as evidenced by the increased expression levels of cleaved caspase-3 and cleaved PARP. Furthermore, an experiment using the USP14 inhibitor IU1 revealed that the inhibition of USP14 activity suppressed 5-fluorouracil (5-FU) resistance in GC cells. Collectively, these findings indicate that USP14 plays critical roles in gastric cancer progression and suggest its potential to serve as a novel therapeutic target for gastric cancer treatment.

• The Korean Journal of Food And Nutrition
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• v.35 no.2
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• pp.127-136
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• 2022

Comparing the quality characteristics of kimchi were measured and anticancer effects using AGS human gastric cancer cells were observed. Five kinds of kimchi samples were made of Kanghwa Baek kimchi (KB), Kangwha Turnip kimchi (KT), Turnip: Chinese cabbage = 1:1 Baek kimchi (T1B1), Turnip:Chinese cabbage = 4:1 Baek kimchi (T4B1), Turnip mul kimchi (T). As a result T kimchi showed the best fermentation characteristics among the five samples. T kimchi had a lower percentage of the total number of aerobic bacteria, while the number of lactobacillus was higher than that of other samples. The mRNA and protein expression levels of apoptosis-related factors found that T kimchi significantly increases the mRNA expression levels of caspases-3 and caspases-9 in AGS human gastric cancer cells as compared to the other kimchi samples. It showed high anticancer effects in the order of T, T1B1, and KB kimchi. As the anticancer effect of Turnip mul kimchi made only of turnip was higher, the higher the turnip content, the higher the anticancer effect. These results show that there were changes in fermentation characteristics such as pH, acidity, number of lactic acid bacteria, and anticancer effects according to the ratio of turnip and cabbage.

• The Korean Journal of Food And Nutrition
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• v.25 no.1
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• pp.64-68
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• 2012

It has been suggested that Helicobacter pylori(H. pylori) infections can promote the development and progression of gastric cancer through the modulation of cell cycle regulators such as $p27^{Kip1}$ and Skp2. $p27^{Kip1}$ is a cyclin-dependent kinase (CDK) inhibitor that blocks the G1/S transition necessary for cell cycle progression. Skp2 is a component of the ubiquitin ligase complex called $SCF^{Skp2}$(SKP1-Cullin-F-box), which specifically binds and promotes the degradation of $p27^{Kip1}$. A low level of $p27^{Kip1}$ and a high level of Skp2 have been reported in many types of cancers, including gastric cancer. In addition, a decrease in $p27^{Kip1}$ has been reported in H. pylori-infected specimens. However, data on Skp2 in H. pylori infections are limited. This study examines the changes in the status of Skp2 in H. pylori-infected gastric epithelial AGS cells. For this, we stimulated AGS cells with H. pylori(NCTC 11637) at the ratio of 300:1(bacterium:cell) for 6 hours. The results of an immunoprecipitation analysis, followed by a western blot, indicate that the interaction between Skp2 and 14-3-3 was elevated 3 hours after the H. pylori treatment. In addition, there was an increase in cytoplasmic Skp2 after 3 hours, whereas there was no change in the nuclear level. Since it has been reported that interaction with 14-3-3 and the subsequent cytoplasmic translocation of Skp2 can increase its protein stability, increases in the interaction with 14-3-3 and the cytoplasmic Skp2 after the H. pylori treatment can increase the level of Skp2 in AGS cells. This phenomenon may explain, at least to some extent, the mechanism underlying the relationship between H. pylori infections and gastric carcinogenesis.