• YAKHAK HOEJI
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• v.56 no.6
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• pp.358-363
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• 2012

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine protein kinase, plays an important role in wide variety of developmental events. NLK phosphorylates T-cell factor/lymphoid enhancer factor (TCF/LEF) transcriptional complex and suppresses wnt signaling pathway through inhibition of ${\beta}$-catenin/TCF complex interaction. However, the function of NLK in gastric carcinogenesis has not been investigated. In the present study, we have examined whether the NLK gene is involved in the development and/or progression of gastric cancers. NLK expression was analyzed by immunohistochemical staining in 153 advanced gastric cancer specimens. Immunhistochemical analysis showed increased expression of NLK in 91 (59.5%) out of 153 gastric cancer specimens. Statistically, there was no significant relationship between altered expression of NLK protein and clinicopathological parameters, including tumor differentiation, location, lymph node metastasis. We identified that mRNA and protein expression of NLK was significantly up-regulated in human gastric cancer tissues compare to corresponding normal gastric tissues. In addition, we found that human gastric cancer cell lines exhibited relatively high expression of NLK, as compared with normal gastric cells. The results of this study suggest that aberrant regulation of NLK may contribute to the development or progression of gastric cancers and serve as a potential biomarker for advanced gastric cancer patients.

• Journal of Gastric Cancer
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• v.20 no.3
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• pp.300-312
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• 2020

Purpose: Circular RNAs (circRNAs) are a new class of RNA molecules whose function is largely unknown. There is a growing evidence that circRNAs play an important regulatory role in the progression of a variety of human cancers. However, the exact roles and the mechanisms of circRNAs in gastric cancer are not clear. In this study, we aimed to elucidate the mechanism of hsa_circ_0005556. Materials and Methods: Real-time quantitative polymerase chain reaction was used to detect the expression of hsa_circ_0005556, miR-4270, and matrix metalloproteinase-19 (MMP19) in gastric cancer tissues and cell lines. The expression of hsa_circ_0005556 in gastric cancer cells was silenced by lentivirus, and cell proliferation, invasion, migration, and tumorigenesis in nude mice were assessed to evaluate the function of hsa_circ_0005556 in gastric cancer. Results: The expression of hsa_circ_0005556 in gastric cancer tissues and gastric cancer cell lines was higher compared to normal controls. In vitro, the downregulation of hsa_ circ_0005556 significantly inhibited proliferation, migration, and invasion of gastric cancer cells. In vivo, the downregulation of hsa_circ_0005556 suppressed tumor growth in nude mice. Conclusions: Our study shows that the hsa_circ_0005556/miR-4270/MMP19 axis is involved in proliferation, migration, and invasion of gastric cancer cells through the competing endogenous RNA (ceRNA) mechanism.

• 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.

• Journal of Microbiology and Biotechnology
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• v.26 no.1
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• pp.28-37
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• 2016

Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer.

• Journal of Microbiology and Biotechnology
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• v.12 no.4
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• pp.664-668
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• 2002

Antioxidants either scavenge superoxide and free radicals or stimulate the detoxification mechanisms within cells, resulting in increased detoxification of free radicals formation. Hyperin, isolated from the stem of Uncaria rhynchophylla, prevented oxygen radical formation and inhibited lipid oxidation. The effective concentrations were 31.3 $\mu$M for a radical scavenging assay and 2.2 $\mu$M for a microsome assay. cDNA microarray analysis to determine which genes were modulated by hyperin found that 50 genes were upregulated and 37 genes were downregulated in SNU-668 human gastric cancer cells. Among these genes, thirteen genes that were significantly affected by hyperin were verified by RT-PCR for their effect of genetic reprogramming.

• 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.

• BMB Reports
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• v.47 no.1
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• pp.39-44
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• 2014

Increasing data shows miR-29a is a key regulator of oncogenic processes. It is significantly down-regulated in some kind of human tumors and possibly functionally linked to cellular proliferation, survival and migration. However, the mechanism remains unclear. In this study, we report miR-29a is significantly under-expressed in gastric cancer compared to the healthy donor. The microvessel density is negatively related to miR-29a expression in gastric cancer tissues. The ectopic expression of miR-29a significantly inhibits proliferation and invasion of gastric cancer cells. Furthermore, western blot combined with the luciferase reporter assays demonstrate that vascular endothelial growth factor A (VEGF-A) is direct target of miR-29a. This is the first time miR-29a was found to suppress the tumor microvessel density in gastric cancer by targeting VEGF-A. Taken together, these results suggest that miR-29a is a tumor suppressor in gastric cancer. Restoration of miR-29a in gastric cancer may be a promising therapeutic approach.

• Biomedical Science Letters
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• v.28 no.2
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• pp.92-100
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• 2022

Ginkgo biloba Leaf Extract (GBE) is an extract from leaves of the Ginkgo biloba tree, widely used as a health supplement. GBE can inhibit the proliferation of several types of tumor cell. Although it is known to have anti-cancer effects in breast cancer and skin cancer, research related to gastric cancer is still insufficient. Based on results showing anti-cancer effects on solid cancer, we aimed to determine whether GBE has similar effects on gastric cancer. In this study, the anti-cancer effect of GBE in gastric adenocarcinoma was investigated by confirming the cell proliferation inhibitory effect of AGS cells. We also evaluated whether GBE regulates expression of the tumor suppressor protein p53 and Rb. GBE has apoptotic effects on AGS cells that were confirmed by changes in anti-apoptosis protein Bcl-2, Bcl-xl and pro-apoptosis protein Bax levels. Wound healing and cell migration were also decreased by treatment with GBE. Furthermore, we verified the effects of GBE on mitogenic signaling by investigating AKT target gene expression levels and revealed downregulated Sod2 and Bcl6 expression. We also confirmed that expression of inflammation-related genes decreased in a time-dependent manner. These results indicate that GBE has an anti-cancer effect on human gastric cancer cell lines. Further research on the mechanism of the anti-cancer effect will serve as basic data for possible anti-cancer drug development.

• Journal of the Korean Society of Food Science and Nutrition
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• v.28 no.5
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• pp.1107-1112
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• 1999

We investigated the inhibitory effects of phytol and methyl 11,14,17 eicosatrienoic acid (methyl ETA, n 3, 20 : 3) separated from perilla leaves on the growth of human cancer cells. Phytol inhibited significantly the growth of HT 29 human colon cancer cells, MG 63 osteosarcoma cells and AZ 521 gastric cancer cells. Although the activity of methyl ETA was lower than that of phytol, it was also observed to have the inhibitory effect on three human cancer cell lines. Furthermore, the DNA synthesis of the MG 63 osteosarcoma cells was markedly decreased by the addition of the phytol and methyl ETA. These results suggest that phytol and methyl ETA identified from the perilla leaves may play a role on the growth inhibition of the human cancer cells.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.305-309
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• 2007

Arsenic compounds have been used to treat various diseases including cancer in oriental medicine. Arsenic trioxide ($As_2O_3,\;Trisenox^{(R)}$) has been used for the treatment of leukemia and its anti-solid tumor activity has also been reported recently. Tetra-arsenic oxide ($As_4O_6,\;TetraAs^{(R)}$) is a newly developed arsenic compound which has shown an anticancer activity in some human cancer cell lines. The purpose of this study was to evaluate the anti-gastric cancer potential of TetraAs and to search for an agent with synergistic interaction with TetraAs against human gastric cancers. We analysed anti-proliferative effect of TetraAs when given alone and in combination with other chemotherapeutic agents such as 5-FU, paclitaxel, and cisplatin in SNU-216, a human gastric cancer cell line. The $IC_{50}$ of these 4 anti-cancer drugs ranged from 5.8 nM to $7.5\;{\mu}M$ with a potency rank of order paclitaxel>TetraAs>cisplatin>5-FU. TetraAs showed 10-fold greater potency than 5-FU and cisplatin at the same effect level of $IC_{50}$. TetraAs+5-FU and TetraAs+paclitaxel showed synergistic and additive interaction, respectively. On the other hand, TetraAs with cisplatin group appeared to be strongly antagonistic. Apoptotic population was measured and compared between single and combination treatment. The apoptotic cells for the combination of TetraAs+5-FU showed significant increase compared to single TetraAs treatment. On the contrary, TetraAs+cisplatin showed less apoptotic cells compared to TetraAs or cisplatin alone treatment. Overall, our results indicate that TetraAs can be effectively combined with 5-FU or paclitaxel, but not with cisplatin for synergistic anti-cancer effect, which warrants further evaluation using in vivo models.