• Molecules and Cells
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• v.28 no.6
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• pp.521-527
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• 2009

Previously, we have reported tissue- and stage-specific expression of miR-372 in human embryonic stem cells and so far, not many reports speculate the function of this microRNA (miRNA). In this study, we screened various human cancer cell lines including gastric cancer cell lines and found first time that miR-372 is expressed only in AGS human gastric adenocarcinoma cell line. Inhibition of miR-372 using antisense miR-372 oligonucleotide (AS-miR-372) suppressed proliferation, arrested the cell cycle at G2/M phase, and increased apoptosis of AGS cells. Furthermore, AS-miR-372 treatment increased expression of LATS2, while over-expression of miR-372 decreased luciferase reporter activity driven by the 3' untranslated region (3' UTR) of LATS2 mRNA. Over-expression of LATS2 induced changes in AGS cells similar to those in AGS cells treated with AS-miR-372. Taken together, these findings demonstrate an oncogenic role for miR-372 in controlling cell growth, cell cycle, and apoptosis through down-regulation of a tumor suppressor gene, LATS2.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.95-105
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• 2020

Purpose: Gastric cancer is a highly metastatic malignant tumor, often characterized by chemoresistance and high mortality. In the present study, we aimed to investigate the role of B-cell lymphoma 3 (Bcl-3) protein on cell migration and chemosensitivity of gastric cancer. Materials and Methods: The gastric cancer cell lines, AGS and NCI-N87, were used for the in vitro studies and the in vivo studies were performed using BALB/c nude mice. Western blotting, wound healing assay, Cell Counting Kit-8 assay, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to evaluate the role of Bcl-3 in gastric cancer. Results: We found that the protein expression of hypoxia (HYP)-inducible factor-1α and Bcl-3 were markedly upregulated under hypoxic conditions in both AGS and NCI-N87 cells in a time-dependent manner. Interestingly, small interfering RNA-mediated knockdown of Bcl-3 expression affected the migration and chemosensitivity of the gastric cancer cells. AGS and NCI-N87 cells transfected with si-RNA-Bcl-3 (si-Bcl-3) showed significantly reduced migratory ability and increased chemosensitivity to oxaliplatin, 5-fluorouracil, and irinotecan. In addition, si-Bcl-3 restored the autophagy induced by HYP. Further, the protective role of si-Bcl-3 on the gastric cancer cells could be reversed by the autophagy inducer, rapamycin. Importantly, the in vivo xenograft tumor experiments showed similar results. Conclusions: Our present study reveals that Bcl-3 knockdown inhibits cell migration and chemoresistance of gastric cancer cells through restoring HYP-induced autophagy.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.201-209
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• 2013

Ginsenoside, one of the active ingredients of Panax ginseng, has a variety of physiologic and pharmacologic effects. The purpose of this study was to explore the effects of ginsenoside Rd (G-Rd) on melastatin type transient receptor potential 7 (TRPM7) channels with respect to the proliferation and survival of AGS and MCF-7 cells (a gastric and a breast cancer cell line, respectively). AGS and MCF-7 cells were treated with different concentrations of G-Rd, and caspase-3 activities, mitochondrial depolarizations, and sub-G1 fractions were analyzed to determine if cell death occurred by apoptosis. In addition, human embryonic kidney (HEK) 293 cells overexpressing TRPM7 channels were used to confirm the role of TRPM7 channels. G-Rd inhibited the proliferation and survival of AGS and MCF-7 cells and enhanced caspase-3 activity, mitochondrial depolarization, and sub-G1 populations. In addition, G-Rd inhibited TRPM7-like currents in AGS and MCF-7 cells and in TRPM7 channel overexpressing HEK 293 cells, as determined by whole cell voltage-clamp recordings. Furthermore, TRPM7 overexpression in HEK 293 cells promoted G-Rd induced cell death. These findings suggest that G-Rd inhibits the proliferation and survival of gastric and breast cancer cells by inhibiting TRPM7 channel activity.

• Nutrition Research and Practice
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• v.5 no.3
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• pp.185-191
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• 2011

In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with $200{\mu}g/mL$ CPE for 24 hr. CPE at various concentrations ($0-200{\mu}g/mL$) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPR exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

• 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.

• Journal of Pharmacopuncture
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• v.16 no.3
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• pp.39-45
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• 2013

Objectives: Buxus Microphylla var. Koreana Nakai Extract (BMKNE) is used as a folk remedy for malaria and veneral disease. In the present study, we investigated the effects of BMKNE in the growth and the survival of AGS cells, the most common human gastric adenocarcinoma cell lines. Methods: The AGS cells were treated with varying concentrations of BMKNE. Analyses of the sub G1 peak, the caspase-3 and -9 activities, and the mitochondrial depolarization were conducted to determine whether AGS cell death occured by apoptosis. Also, to identify the role of transient receptor potential melastatin (TRPM) 7 channels in AGS cell growth and survival, we used human embryonic kidney (HEK) 293 cells overexpressed with TRPM7 channels. Results: Experimental results showed that the sub G1 peak, the caspase-3 and -9 activities, and the mitochondrial depolarization were increased. Therefore, BMKNE was found to induce the apoptosis of these cells, and this apoptosis was inhibited by SB203580 (a p38 mitogen-activated protein kinase (MAPK) inhibitor), and by a c-jun NH2-terminal kinase (JNK) II inhibitor. Furthermore, BMKNE inhibited TRPM7 currents and TRPM7 channel over-expressions in HEK 293 cells, exacerbating BMKNE-induced cell death. Conclusions: These findings indicate that BMKNE inhibits the growth and the survival of gastric cancer cells due to a blockade of the TRPM7 channel's activity and MAPK signaling. Therefore, BMKNE is a potential drug for treatment of gastric cancer, and both the TRPM7 channel and MAPK signaling may play an important role in survival in gastric cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.4
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• pp.633-640
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• 2004

This study was performed to investigate the cytotoxic effect of the water-extract from Chaga mushroom (Inonotus obliquus) compositions containing powdered green tea in HCT-15 human colon carcinoma, AGS human gastric carcinoma and NIH3T3 mouse normal fibroblast cells using viable cell count and MTT assay. The water-extract from Chaga mushroom compositions induced inhibitory effects on proliferation of HCT-15 and AGS cells in the MTT assay and viable cell count. However, mouse normal NIH3T3 cells were exhibited 80% survival under the same condition. Chaga mushroom compositions showed highly antiproliferative effect in human cancer cell line HCT-15 and AGS, but not in mouse normal cell line NIH3T3. These results suggest that Chaga mushroom (Inonotus obliquus) compositions containing powdered green tea are the candidate for chemoprevention in colon and gastric cancer.

• Herbal Formula Science
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• v.30 no.2
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• pp.59-66
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• 2022

Objectives : This study is to investigate whether Carthami flos exhibits a synergistic effect on the apoptotic effect of doxorubicin on human gastric cancer cells. Methods : We used AGS, a human gastric cancer cell line. To investigate the apoptotic efficacy of doxorubicin and Carthami flos, MTT and CCK-8 methods were used. To confirm apoptosis, cell cycle and mitochondrial membrane potential changes were confirmed. To investigate the mechanism of apoptosis, the reactive oxygen species (ROS) experiment was performed. Results : 1. Doxorubicin or Carthami flos induced cell death in the human gastric cancer cell line AGS. 2. Carthami flos showed a synergistic effect of cell death by doxorubicin. 3. The cell cycle and mitochondrial membrane potential changes revealed that cell death was apoptosis. 4. Apoptosis was related to reactive oxygen species (ROS) generation. Conclusions : This result shows the anticancer synergistic effect of Carthami flos in gastric cancer cells, and is considered to be an important basis for the development of anticancer drugs for Carthami flos.

• BMB Reports
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• v.46 no.1
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• pp.25-30
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• 2013

Gap junctions and their structural proteins, connexins (Cxs), have been implicated in carcinogenesis. To explore the involvement of Cx32 in gastric carcinogenesis, immunochemical analysis of Cx32 and proliferation marker Ki67 using tissue-microarrayed human gastric cancer and normal tissues was performed. In addition, after Cx32 overexpression in the human gastric cancer cell line AGS, cell proliferation, cell cycle analyses, and $p21^{Cip1}$ and $p27^{Kip1}$ expression levels were examined by bromodeoxyuridine assay, flow cytometry, real-time RT-PCR, and western blotting. Immunohistochemical study noted a strong inverse correlation between Cx32 and Ki67 expression pattern as well as their location. In vitro, overexpression of Cx32 in AGS cells inhibited cell proliferation significantly. $G^1$ arrest, up-regulation of cell cycle-regulatory proteins $p21^{Cip1}$ and $p27^{Kip1}$ was also found at both mRNA and protein levels. Taken together, Cx32 plays some roles in gastric cancer development by inhibiting gastric cancer cell proliferation through cell cycle arrest and cell cycle regulatory proteins.

• Korean Journal of Oriental Medicine
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• v.18 no.1
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• pp.85-92
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• 2012

Objective : The purpose of this study was to investigate the anti-cancer effects of Sophorae Radix and the effects of 5-Fluorouracil (5-FU) in human gastric adenocarcinoma cells (AGS). Method : We used human gastric adenocarcinoma cell line, AGS cells. We examined cell death by MTT assay and caspase 3 assay with Sophorae Radix. To examine the inhibitory effects of Sophorae Radix, cell cycle (sub G1) analysis was done the AGS cells after three days with Sophorae Radix. The reversibility of Sophorae Radix was examined on one day to five days treatment with 100 ${\mu}g/ml$ Sophorae Radix. Result : Sophorae Radix inhibited the growth of AGS cells in a dose-dependent fashion. Also we showed that Sophorae Radix induced apoptosis in AGS cells by MTT assay, caspase 3 assay and sub-G1 analysis. Sophorae Radix combined with 5-FU markedly inhibited the growth of AGS cells compared to Sophorae Radix or 5-FU alone. After 3 days treatment of AGS cells with Sophorae Radix, the fraction of cells in sub-G1 phase was much higher than that of the control group. Conclusion : Our findings provide insight into unraveling the effects of Sophorae Radix in human gastric adenocarcinoma cells and developing therapeutic agents against gastric cancer.