• The Korea Journal of Herbology
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• v.28 no.6
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• pp.155-160
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• 2013

Objectives : Gastric cancer is a leading cause of cancer-related deaths, worldwide. Houttuynia cordata Thunberg (H. cordata) has been used as a medicinal plants and it has an anti-cancer activity in human colorectal cancer and leukemic cancer. However, the potential anti-cancer activity and mechanisms of H. cordata for human gastric cancer cells have not been tested so far. Thus, this study examined the biological effects of H. cordata on the human gastric cancer cell line SNU-1 and AGS. Methods : Inhibition of cell proliferation and cell cycle by H. cordata was carried out by MTT assay and Muse cell cycle analysis and the expressions of protein associated with apoptosis and cell cycle regulation were investigated with Western blot analysis. Results : In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by H. cordata in a time and dose dependent manner, Inhibition of cell proliferation by H. cordata was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bax to Bcl-2 by H. cordata. Also, H. cordata regulated the expression of cell cycle regulatory proteins such as pRb, cyclin D1, cyclin E, CDK4, CDK2, p21 and p15. Conclusion : The antiproliferative effect of H. cordata on SNU-1 and AGS gastric cancer cells revealed in this study suggests that H. cordata has intriguing potential as a chemopreventive or chemotherapeutic agent.

• Korean Journal of Veterinary Research
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• v.15 no.2
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• pp.223-231
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• 1975

In mammals there are two distinct cellular units of the gastric glands which are responsible for the secretion of acid and pepsin respectively, namely, the parietal cells for acid and the peptic or chief cells for pepsin. On the other hand, the bird does net have separate parietal and chief cells in the glandular stomach. There exist only a single cell type in the asian gastric secretory-glands. In spite of this single cell type, however, variation in pepsin and acid secretion can he seen. Present study was conducted to know distribution, secretion and formation of the pepsinogen granules in chicken and rat stomach which observing by light and electron microscope. 1. In chicken, the pepsinogen granules are distributed in all submucosal gland cells and yet there are no distinction of parietal and chief cells. In rat, the pepsinogen granules are distributed in chief cells which lined the lower two-thirds of the gastric tubles and the parietal cells occupy upper third of the tuble. 2. Carbachol markedly stimulates the secretion of pepsinogen granules in chiken and rat, but Histamine is slightly. 3. After Histamine and Carbachol treatment, the pepsinogen granules are formated continuously and reaccmulated as control after 3 to 4 hours.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.939-949
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• 2008

Objective : This study was carried out to investigate the effects of Jisildochehwan extract on indomethacin-induced gastric mucosal lesions of mice. as compared with misoprostol. Methods : Experimental mice were classified into four groups. No gastro-inflammation elicited mice were the normal group(NOR). Gastro-inflammation elicited mice were the control group (CON). Misoprostol-administered mice after gastro-inflammation elicitation were the misoprostol-administered group (MA). Jisildochehwan-administered mice after gastro-inflammation elicitation were the Jisildochehwan-administered group(JA). In this study, we examined superoxide dismutase(SOD) ability, anti-inflammatory ability arrangement of mucous-secreted cells. distribution of mucosal neck cells, mucosal surface cells. neutral mucous-secreted cells. PAS reaction. COX-1, $TNF-{\alpha}$, $NF-{\kappa}B$ p65 and iNOS. Results : The SOD ability of the Jisildochehwan group increased dose-dependently. The hemorrhagic erosion and the damage of arrangement of mucous-secreted cells increased in the CON group. but decreased in the MA and JA groups. The COX-1 positive were decreased in the CON group, but increased in the MA and JA groups. The distribution of mucosal neck cells and mucosal surface cells. PAS positive reaction of surface mucous cells were decreased in CON group, but increased in MA and JA group. $TNF-{\alpha}$, $NF-{\kappa}B$ p65 and iNOS increased in the CON group, but decreased in the MA and JA groups. In all the results, the effects were better in the JA group than in the MA group. Conclusion : Jisildochehwan extract was more effective than Misoprostol. Jisildochehwan has excellent protective effects on indomethacin-induced gastric mucosal lesions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.29 no.2
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• pp.195-201
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• 2015

The aim of the study is to investigate the anti-cancer effects of Scutellaria barbata in AGS human gastric adenocarcinoma cells. MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and caspase 3 or 9 activity assay were carried out to examine cell death with Scutellaria barbata. To elucidate the inhibitory effects of Scutellaria barbata, cell cycle (sub-G1) analysis and mitochondrial membrane potential were performed in AGS cells after 24 h incubation with Scutellaria barbata. Scutellaria barbata induced apoptosis in AGS cells by using the MTT assay, the sub-G1 analysis and mitochondrial membrane potential assay. The stronger inhibition effects of AGS cell growth was observed by application of Scutellaria barbata combined with several anti-cancer drugs (paclitaxel, 5-fluorouracil, cisplatin, ectoposide, doxorubicin and docetaxel) in comparison to the application of Scutellaria barbata or anti-cancer drugs. Our findings provide insight into unraveling the effects of Scutellaria barbata in human gastric cancer cells and developing therapeutic agents against gastric cancer.

• Applied Microscopy
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• v.28 no.2
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• pp.225-236
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• 1998

Adriamycin is a one of anthracyclin antibiotics isolated from the culture media of Streptomyces peucetius var casius. The formation of reactive oxygen metabolite by redox cycling during the metabolism and the inhibition of DNA synthesis results in antineoplastic effects of adriamycin. The authors have demonstrated the effects of SOD(superoxide dismutase) or DMTU (dimethyl thiourea), which are used as an antioxidant, on the ultrastructural changes of the gastric chief cells after the administration of adriamycin in the rat. Adriamycin (30 mg/kg) was administered intraperitoneally to the Sprague-Dawley rats weighing about 220 gm and SOD (15000 unit/kg) or DMTU (500 mg/kg) were administered intraperitoneally to the rats 30 minutes after the administration of adriamycin. The gastric chief cells 24, 48 and 72 hours after the administration of adriamycin were observed with Hitachi-600 electron microscope. The results were as follows. 1. SOD or DMTU alone did not affect the ultra structures of the gastric chief cells in the rat. 2. Dilation, sacculation and segmentation of the cisternae of rough endoplasmic reticulum, dilation of the saccules of Golgi complex and dilated mitochondria with electron lucent matrix were seen in the adriamycin treated rats. In the course of time, the ultrastructures of the chief cell changed markedly. 72 hours after drug administration, severely dilated cisternae of rough endoplasmic reticulum, with clumping of chromatin around the nuclear envelope and mitochondria with electron lucent matrix and dilated cristae were seen in the chief cell. 3. The treatment of SOD is more effective than DMTU to attenuated the ultrastructural changes of the chief cells in the adriamycin administered rat. Consequently it is suggested that adriamycin would induce the degenerative changes of the organelles of the chief cell. The treatment of SOD is more effective than DMTU to attenuate the adriamycin induced damage.

• Journal of Gastric Cancer
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• v.22 no.4
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• pp.319-338
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• 2022

Purpose: Gastric cancer (GC) has high morbidity and mortality, the cure rate of surgical treatment and drug chemotherapy is not ideal. Therefore, development of new treatment strategies is necessary. We aimed to identify the mechanism underlying Sp1 regulation of GC progression. Methods and Methods: The levels of Sp1, β-catenin, SET domain bifurcated 1 (SETDB1), and 15-hydroxyprostaglandin dehydrogenase (HPGD) were detected by quantitative reverse transcription polymerase chain reaction and western blot analysis. The targets of SETDB1 were predicted by AnimalTFDB, and dual-luciferase reporter assay was used for confirming the combination of Sp1, β-catenin, and SETDB1. HGC27 or AGS cells (1×10⁶ cells/mouse) were injected into mice via the caudal vein for GC model establishment. The level of Ki67 was detected using immunohistochemistry, and hematoxylin and eosin staining was performed for evaluating tumor metastasis in mice with GC. Results: HPGD was inhibited, while the protein levels of Sp1, β-catenin, and SETDB1 were up-regulated in GC tissues and cell lines. HPGD overexpression or SETDB1 silencing inhibited the proliferation, invasion, and migration of GC cells, and Sp1 regulated the proliferation, invasion, and migration of GC cells in a β-catenin-dependent manner. Furthermore, HPGD served as a target of SETDB1, and it was negatively regulated by SETDB1; additionally, Sp1 and β-catenin bound to the SETDB1 promoter and negatively regulated HPGD expression. We proved that Sp1 regulated GC progression via the SETDB1/HPGD axis. Conclusions: Our findings revealed that Sp1 transcriptionally inhibited HPGD via SETDB1 in a β-catenin-dependent manner and promoted the proliferation and metastasis of GC cells.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.219-226
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• 2023

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOP-induced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

• Molecules and Cells
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• v.46 no.8
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• pp.476-485
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• 2023

Gastric cancer stem-like cells (GCSCs) possess stem cell properties, such as self-renewal and tumorigenicity, which are known to induce high chemoresistance and metastasis. These characteristics of GCSCs are further enhanced by autophagy, worsening the prognosis of patients. Currently, the mechanisms involved in the induction of stemness in GCSCs during autophagy remain unclear. In this study, we compared the cellular responses of GCSCs with those of gastric cancer intestinal cells (GCICs) whose stemness is not induced by autophagy. In response to glucose starvation, the levels of β-catenin and stemness-related genes were upregulated in GCSCs, while the levels of β-catenin declined in GCICs. The pattern of deubiquitinase ubiquitin C-terminal hydrolase-L3 (UCH-L3) expression in GCSCs and GCICs was similar to that of β-catenin expression depending on glucose deprivation. We also observed that inhibition of UCH-L3 activity reduced β-catenin protein levels. The interaction between UCH-L3 and β-catenin proteins was confirmed, and it reduced the ubiquitination of β-catenin. Our results suggest that UCH-L3 induces the stabilization of β-catenin, which is required to promote stemness during autophagy activation. Also, UCH-L3 expression was regulated by c-Fos, and the levels of c-Fos increased in response to autophagy activation. In summary, our findings suggest that the inhibition of UCH-L3 during nutrient deprivation could suppress stress resistance of GCSCs and increase the survival rates of gastric cancer patients.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.239-244
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• 2012

This study examined the inhibitory effects of 4-guanidinobutyric acid (4GBA), an alkaloid, against gastric lesions by assessing the inhibition of Helicobacter pylori (H. pylori) and gastric cancer cells. Acute and chronic gastritis were also observed using HCl/ethanol (EtOH) and indomethacin-induced gastric lesion models, respectively. 4GBA inhibited the growth of H. pylori in a dose dependent manner, and showed acid-neutralizing capacity. In the pylorus ligated rats, 4GBA decreased the volume of gastric secretion and gastric acid output slightly, and increased the pH. 4GBA at a dose of 100 mg/kg reduced the size of HCl/EtOH-induced gastric lesions (70.8%) and indomethacin-induced gastric lesions (38.8%). The antigastritic action of 4GBA might be associated with the acid-neutralizing capacity, anti-H. pylori action, and decreased volume of gastric secretion. These results suggest that 4GBA might be useful in the treatment and/or protection of gastritis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1077-1082
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• 2015

Recent studies have suggested that the RAS protein activator like-1 (RASAL1) functions as a tumor suppressor in vitro and may play an important role in the development of gastric cancer. However, whether or not RASAL1 suppresses tumor growth in vivo remains to be determined. In the present study, we investigated the role of RASAL1 in gastric carcinogenesis using an in vivo xenograft model. A lentiviral RASAL1 expression vector was constructed and utilized to transfect the human poorly differentiated gastric adenocarcinoma cell line, BGC-823. RASAL1 expression levels were verified by quantitative real-time RT-PCR and Western blotting analysis. Then, we established the nude mice xenograft model using BGC-823 cells either over-expressing RASAL1 or normal. After three weeks, the results showed that the over-expression of RASAL1 led to a significant reduction in both tumor volume and weight compared with the other two control groups. Furthermore, in xenograft tissues the increased expression of RASAL1 in BGC-823 cells caused decreased expression of p-ERK1/2, a downstream moleculein the RAS/RAF/MEK/ERK signal pathway. These findings demonstrated that the over-expression of RASAL1 could inhibit the growth of gastric cancer by inactivation of the RAS/RAF/MEK/ERK pathway in vivo. This study indicates that RASAL1 may attenuate gastric carcinogenesis.