• Journal of Life Science
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• v.26 no.7
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• pp.847-854
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• 2016

Cordycepin, a derivative of the nucleoside adenosine, is one of the active components extracted from fungi of genus Cordyceps, and has been shown to have many pharmacological activities. In this study, we investigated the effects of cordycepin on proliferation and apoptosis of human gastric cancer AGS cells, and its possible mechanism of action. Treatment of cordycepin resulted in significant decrease in cell viability of AGS cells in a concentration-dependent manner. A concentration-dependent apoptotic cell death was also measured by agarose gel electrophoresis and flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled cordycepin treatment resulted in an enhanced expression of tumor necrosis factor-related apoptosis-inducing ligand, death receptor 5 and Fas ligand. Furthermore, up-regulation of pro-apoptotic Bax, and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL expression were also observed in cordycepin-treated AGS cells. These were followed by activation of caspases (caspase-9, -8 and -3), subsequently leading to poly (ADP-ribose) polymerase cleavage. Taken together, these findings indicate that cordycepin induces apoptosis in AGS cells through regulation of multiple apoptotic pathways, including death receptor and mitochondria. Although further mechanical studies are needed, our results revealed that cordycepin can be regarded as a new effective and chemopreventive compound for human gastric cancer treatment.

• Korean Journal of Acupuncture
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• v.29 no.2
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• pp.271-289
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• 2012

Objectives : Ganoderma lucidum(Ganoderma or lingzhi, 靈芝) is a well-known oriental medical mushroom containing many bioactive compounds. The possible mechanisms involved in its effects on cancer cells remain to be elucidated. In the present study, the anti-proliferative and apoptotic activities of the G. lucidum ethanol extract(GEE), in AGS human gastric cancer cells were investigated. Methods : It was found that exposure of AGS cells to GEE resulted in the growth inhibition in a dose and time dependent manner as measured by trypan blue count and MTT assay. The anti-proliferative effect of GEE treatment in AGS cells was associated with morphological changes and formation of apoptotic bodies, and the flow cytometry analysis confirmed that GEE treatment increased the populations of apoptotic-sub G1 phase. Growth inhibition and apoptosis of AGS cells by GEE were connected with a concentration and time-dependent up-regulation of tumour necrosis factor-related apoptosis-inducing ligand(TRAIL) expression. Results : The levels of XIAP and survivin expression, members of IAP family proteins, were gradually down-regulated by GEE treatment. However other members of IAP family proteins such as cIAP-1 and cIAP-2 remained unchanged in GEE-treated AGS cells. GEE treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9 and a concomitant degradation of poly(ADP-ribose) polymerase(PARP) protein, a caspase-3 substrate protein. Additionally, GEE-induced apoptosis was associated with the inhibition of Akt activation in a concentration and time-dependent manner, and pre-treatment with LY294002, a phosphoinositide 3-kinase(PI3K)/Akt inhibitor, significantly increased GEE-induced growth inhibition and apoptosis. Conclusions : Therefore, G. lucidum has a strong potential as a therapeutic agent for preventing cancers such as gastric cancer cells.

• 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.

• Preventive Nutrition and Food Science
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• v.4 no.2
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• pp.113-116
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• 1999

The anticancer effect of methanol extracts from common Chinese cabbage kimchi(CC kimchi ) and organically cultivated Chinese cabbage kimchi (OC kimchi) was studied on the cell growth, MTT assay and SRB assay using AGS human gastric cancer cells. Methanol extracts from CC kimchi and OC kimchi exhibited the anticancer activites in vitro and in vivo. Methanol extract from 6 day-fermented CC kimchi and OC kimchi inhibited the growth of AGS cells by 55.2 and 60.7% , respectively. At MTT assay an dSRB assay, 6 day-fermented OC kimchi showed higher inhibition rate (MTT : 42%, SRB : 61%) than 6 day-fermented CC kimchi(MTT : 33%, SRB : 52%). Methanol extracts from 6-day fermented CC kimchi and OC reduced the tumor formation and prolonged the life span of sarcoma-180 cell injected Balb.c mouse. OC kimchi treated group resulted in the smaller tumor weight of 4.58$\pm$0.32g compared th the CC kimchi group of 5.40$\pm$0.78g and the control group of 7.50$\pm$0.54g and OC kimchi treted group (25.3 days) lived longest among control (20.2days ) and CC kimchi(23.5days) treted groups.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.26-32
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• 2015

Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying concentrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at $70{\mu}g/mL$, 15.94% at $140{\mu}g/mL$, 26.56% at $210{\mu}g/mL$ and 38.08% at $280{\mu}g/mL$). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.

• Toxicological Research
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• v.21 no.2
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• pp.107-113
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• 2005

[ $BARODON^{(R)}$ ] is a multi-purpose, high functional alkali solution made by mixing and liquid-ionizing silicon, calcium, sodium, borax, organic carbon chemicals and silver. In this study, we have investigated the apoptotic potential and mechanistic insights of $BARODON^{(R)}$ in human gastric cancer cell line (AGS cells). In MTT assay, $BARODON^{(R)}$ reduced cell viability in AGS cells. Morphological features of apoptosis with marked cytoplasmic vacuolation and appearance of apoptotic peaks in flow cytometry were observed in AGS cells with$BARODON^{(R)}$ treatment. In addition, $BARODON^{(R)}$ induced apoptosis of stomach cancer cell is related to bax up-regulation, caspase 7 protease activation and subsequent cleavage of poly (ADP-ribose) polymerase (PARP). These results suggest that BARODON can induce the apoptosis of AGS cells through modulation of bcl-2 family and the activation of intrinsic caspase cascades, indicating that it is potentially useful as a anti-cancer agent.

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.207-213
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• 2016

Little information about the biological activities of Citrus limon (lemon) leaves has been reported, whereas the fruit of Citrus limon (lemon) has been well-documented to contain various pro-health bio-functional compounds. In the present study, the antiproliferative activities of the lemon leaves were evaluated using several cancer cell lines. From the n-hexane, chloroform, ethyl acetate, n-butanol, and water fractions of methanolic extract of the leaves, the chloroform fraction of lemon leaves (CFLL) showed the most potent antiproliferative activity in the AGS human gastric cancer cells. The current study demonstrates that CFLL induces apoptosis in AGS cells, as evidenced by an increase in apoptotic bodies, cell population in the sub-G1 phase, Bax/Bcl-2 ratio, and cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-9. Compositional analysis of the CFLL using gas chromatography mass spectrometry (GC-MS) resulted in the identification of 27 compounds including trans, trans-farnesol (3.19 %), farnesol (3.26 %), vanillic acid (1.45 %), (-)-loliolide (5.24 %) and palmitic acid (6.96 %). Understanding the modes of action of these compounds individually and/or synergistically would provide useful information about their applications in cancer prevention and therapy.

• Journal of Ginseng Research
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• v.38 no.1
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• pp.22-27
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• 2014

Background: Research has been conducted with regard to the development of methods for improving the pharmaceutical effect of ginseng by conversion of ginsenosides, which are the major active components of ginseng, via high temperature or high-pressure processing. Methods: The present study sought to investigate the anticancer effect of heat-processed American ginseng (HAG) in human gastric cancer AGS cells with a focus on assessing the role of apoptosis as an important mechanistic element in its anticancer actions. Results and Conclusion: HAG significantly reduced the cancer cell proliferation, and the contents of ginsenosides Rb1 and Re were markedly decreased, whereas the peaks of less-polar ginsenosides [20(S,R)-Rg3, Rk1, and Rg5] were newly detected. Based on the activity-guided fractionation of HAG, ginsenoside 20(S)-Rg3 played a key role in inducing apoptosis in human gastric cancer AGS cells, and it was generated mainly from ginsenoside Rb1. Ginsenoside 20(S)-Rg3 induced apoptosis through activation of caspase-3, caspase-8, and caspase-9, as well as regulation of Bcl-2 and Bax expression. Taken together, these findings suggest that heat-processing serves as an increase in the antitumor activity of American ginseng in AGS cells, and ginsenoside 20(S)-Rg3, the active component produced by heat-processing, induces the activation of caspase-3, caspase-8, and caspase-9, which contributes to the apoptotic cell death.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1843-1849
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• 2004

Conventional medicines have usually sorted to a number of treatments such asoperation, radiotherapy, and chemotherapy. The existing anti-cancer agents, designed to eradicate cancer cells, have strong toxicities, also with leading to harmful side effects. Recently, a number of researches on natural products have been actively carried out in efforts to develop new treatments that can decrease side effects or increase anti-cancer effects. We performed this study to understand the molecular basis underlying the antitumor effects of Pharbitis nil, and Plantago asiatica, which have been used for herbal medicinal treatments against cancers in East Asia. We analyzed the effects of these medicinal herbs on proliferation and on expression of cell growth/apoptosis related molecules, with using an AGS gastric cancer cell line. The treatment of Pharbitis nil dramatically reduced cell viabilities in a dose and time-dependent manner, but Plantago asiatica didn't. FACS analysis and Annexin V staining assay also showed that Pharbitis nil induce apoptotic cell death of AGS. Expression analyses via RT-PCR and Western blots revealed that Pharbitis nil didn't increase expression of the p53 and its downstream effector p21/sup wafl/, and that the both increased expression of apoptosis related Sax and cleavage of active caspase-3 protein. We also confirmed the translocation of Sax to mitochondria. Collectively, our data demonstrate that Pharbitis nilinduce growth inhibition and apoptosis of human gastric cancer cells, and these effects are correlated with down- and up-regulation of growth-regulating apoptotic and tumor suppressor genes, respectively.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.84-95
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• 2006

Costunolide is an active sesquiterpene lactone isolated from the root of Saussurea lappa Clarke and is known to exhibit a variety of biological activities, including anti-carcinogenic and anti-inflammatory effects. Nevertheless, the pharmacological pathways of costunolide have not yet been fully elucidated. In this study, its cytotoxic effects were examined using AGS gastric cancer cells. Its treatment resulted in apoptosis in a dose- and time-dependent manner. The effects were attributed to the regulation of pro-apoptotic molecules and suppression of anti-apoptotic molecules. These results suggest that costunolide may be a candidate to deal with gastric cancers by chemopreventive agents.