• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.501-509
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• 2016

Shikonin, which derives from Lithospermum erythrorhizon, has been traditionally used against a variety of diseases, including cancer, in Eastern Asia. Here we determined that shikonin inhibits proliferation of gastric cancer cells by inducing apoptosis. Shikonin's biological activity was validated by observing cell viability, caspase 3 activity, reactive oxygen species (ROS) generation, and apoptotic marker expressions in AGS stomach cancer cells. The concentration range of shikonin was 35-250 nM with the incubation time of 6 h. Protein levels of Nrf2 and p53 were evaluated by western blotting and confirmed by real-time PCR. Our results revealed that shikonin induced the generation of ROS as well as caspase 3-dependent apoptosis. c-Jun-N-terminal kinases (JNK) activity was significantly elevated in shikonin-treated cells, thereby linking JNK to apoptosis. Furthermore, our results revealed that shikonin induced p53 expression but repressed Nrf2 expression. Moreover, our results suggested that there may be a co-regulation between p53 and Nrf2, in which transfection with siNrf2 induced the p53 expression. We demonstrated for the first time that shikonin activated cell apoptosis in AGS cells via caspase 3- and JNK-dependent pathways, as well as through the p53-Nrf2 mediated signal pathway. Our study validates in partly the contribution of shikonin as a new therapeutic approaches/agent for cancer chemotherapy.

• Food Science and Preservation
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• v.19 no.2
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• pp.278-286
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• 2012

The growth inhibition effect of $Doenjang$ that was prepared with various kinds of solar salt was investigated. $Doenjang$ was prepared using the bacterial koji and five kind of salt with 12% salt concentration (w/w): purified salt $Doenjang$, one-year aged solar salt $Doenjang$, four-year aged solar salt $Doenjang$, topan solar salt $Doenjang$, and boiled solar salt $Doenjang$. The $Doenjangs$ were fermented and aged for 18 months. The growth inhibition effects of the water extracts and the methanol extracts of the $Doenjangs$ were measured on AGS human gastric adenocarcinoma cells, HT-29 colon carcinoma cells, and BJ human foreskin normal cells using MTT assay. The water and methanol extracts of the $Doenjang$ samples showed growth inhibition effects on the cancer cells, in the following order of the samples with the strongest to the weakest effect: the four-year aged solar salt $Doenjang$, the topan solar salt $Doenjang$, the boiled solar salt $Doenjang$, the one-year aged solar salt $Doenjang$, and the purified salt $Doenjang$. The methanol extracts of the four-year aged solar salt Doenjang (AGS: 55% and HT-29: 48%) showed the strongest growth inhibition effect. In addition, decreased cancer cell numbers and morphological changes in the cancer cells (AGS and HT-29) were observed when the methanol extract of the four-year aged solar salt $Doenjang$ was treated. None of the $Doenjang$ extracts showed a growth inhibition effect on the BJ normal cells, though.

• Journal of Mushroom
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• v.12 no.4
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• pp.304-310
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• 2014

The use of mushrooms has immense potential in many diverse applications. Until now, more than 3,000 species are consumed around the world, and more than 100 have shown promising clinical activity against cancer and other chronic diseases. Sparassis latifolia (formerly S. crispa) is an edible mushroom that harbors ${\beta}$-glucan reported to possess immunostimulatory and anticancer properties. However there have been no reports on the anticancer activity of hydrophobic fractions of S. latifolia. In this study, the anticancer activities of S. latifolia extract and hydrophobic fractions were investigated using AGS (stomach cancer), A529 (lung cancer), and HepG2 (liver cancer) cell lines. In cytotoxicity results of A529 cells, fractions of A2, A3, A4, A6, A7, A8, A9, and A10 in all 12 fractions show low $IC_{50}$ values. For HepG2 cells, A7 fraction results in the lowest $IC_{50}$ value while A7, A8, and A11 fractions show low $IC_{50}$ values in AGS cells. S. latifolia extract lead to low cell viability in cancer cells, compared to positive control of paclitaxel. A compound with molecular weight of 181 were detected using HPLC-MS but not identified yet. As a result, the hydrophobic fractions of S. latifolia EtOH extract would be a possible candidate as natural anticancer agents in the future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.4
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• pp.417-425
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• 2017

Cnidium monnieri (L.) Cusson is distributed in China and Korea, and the fruit of C. monnieri is used as traditional Chinese medicine to treat carbuncle and pain in female genitalia. In this study, we examined the anti-proliferation and cell cycle arrest effects of ethanol extracts from C. monnieri (CME) in AGS gastric cancer cells. Our results show that CME suppressed cell proliferation and induced release of lactate dehydrogenase (LDH) in AGS cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and LDH assay. Cell morphology was altered by CME in a dose-dependent manner. In order to identify the cell cycle arrest effects of CME, we investigated cell cycle analysis after CME treatment. In our results, CME induced cell cycle arrest at G1 phase. Protein kinase B (Akt) plays a major role in cell survival mechanisms such as growth, division, and metastasis. Akt protein regulates various downstream proteins such as glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and tumor protein p53 (p53). Expression levels of p-Akt, p-GSK-$3{\beta}$, p53, p21, cyclin E, and cyclin-dependent kinase 2 (CDK2) were determined by Western blot analysis. Protein levels of p-Akt, p-GSK-$3{\beta}$, and cyclin E were reduced while those of p53, p21, and p-CDK2 (T14/Y15) were elevated by CME. Moreover, treatment with CME, LY294002 (phosphoinositide 3-kinase/Akt inhibitor), BIO (GSK-$3{\beta}$ inhibitor), and Pifithrin-${\alpha}$ (p53 inhibitor) showed that cell cycle arrest effects were mediated through regulation of the Akt/GSK-$3{\beta}$/p53 signaling pathway. These results suggest that CME induces cell cycle arrest at G1 phase via the Akt/GSK-$3{\beta}$/p53 signaling pathway in AGS gastric cancer cells.

• 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.

• 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.

• Food Science and Preservation
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• v.21 no.6
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• pp.878-884
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• 2014

Increased antimutagenic and in vitro anticancer effects were observed by the fermentation process during Kochujang manufacturing. In order to confirm the increased functionality, wheat grain, first fermented wheat grains (FFWG), second fermented wheat grains (SFWG), final fermented wheat grains (FiFWG), red pepper powder (RPP), and commercial Kochujang (CK) were prepared. Kochujang manufactured with final fermented wheat grains and red pepper powder were further fermented for 15 days and 30 days. The antimutagenic effects were determined by counting the number of revertants in Salmonella Typhimurium TA100 against N-methyl-N'-nitro-nitrosoguanidine (MNNG, 1.0mg/mL). The final fermented wheat grains (52% inhibition) showed higher antimutagenic effects than the wheat grain (34%), and the commercial Kochujang showed the highest antimutagenic effects (55%). We tested the inhibitory effect on the growth of HT-29 human colon carcinoma cells and AGS human gastric adenocarcinoma cells by using MTT (3-(4,5-dimethyl-thiazol)-2,5-diphenyltetrazolium bromide) assay. The results showed that increased fermentation process continually increased the growth inhibitory effect on both cancer cells. The further fermentation for 15 days of the Kochujang product also increased inhibitory growth of the AGS cancer cells. In conclusion, the methanol extract from fermented wheat grains and commercial Kochujang showed sequentially increased antimutagenic and in vitro anticancer activity, and thus the final commercial Kochujang revealed the highest effect.

• KSBB Journal
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• v.27 no.4
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• pp.227-231
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• 2012

Whole plants of Zostera asiatica were extracted twice with acetone/methylene chloride (A+M) and methanol (MeOH) in turn. The combined crude extracts were evaporated in vacuo and then the residue was partitioned between water and methylene chloride. The aqueous layer was fractionated into $H_2O$ and n-butanol and then the organic layer was also fractionated into 85% aq. MeOH and n-hexane, successively. The crude extracts and their solvent fractions were evaluated for their inhibitory effect on growth of human cancer cells AGS, HT-29, MCF-7, and HT-1080 cells by MTT reduction assay. Among samples tested, 85% aq. MeOH and n-hexane fractions showed strong cytotoxic effect against AGS, HT-29, and MCF-7 cells. On the other hand, for HT-1080 cell, 85% aq. MeOH fraction exhibited the strongest cytotoxic effect.

• Preventive Nutrition and Food Science
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• v.12 no.2
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• pp.84-88
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• 2007

In this study, we investigated antimutagenic and anticancer activities of leaf mustard (LM, Brassica juncea) and leaf mustard kimchi (LMK) during their fermentation period. Methanol extracts were prepared from raw mustard, brined leaf mustard in 10% Gueun salt solution for 2 hrs, leaf mustard fermented at 15$^{\circ}C$ for 5 days after brined in 10% Guenun salt solution for 2 hrs (Fr-LM), fresh leaf mustard kimchi (Fresh-LMK) and optimally ripened leaf mustard kimchi fermented at 5$^{\circ}C$ for 30 days (OR-LMK). OR-LMK showed the strongest inhibitory activities against the mutagenicities induced by aflatoxin B1 in Salmonella Typhimurium TA100. LMs and LMKs inhibited the survival or growth of AGS human gastric adenocarcinoma cells and HT-29 human colon carcinoma cells in MTT assay and growth inhibition test. Among the extracts, OR-LMK and FR-LM exhibited strong antiproliferative effect against cancer cells, especially HT-29 cells. DAPI staining assay showed that OR-LMK induced apoptosis cell death of HT-29 cells in a dose-dependent manner. These results suggest that leaf mustards and leaf mustard kimchi have chemopreventive activities.

• The Korean Journal of Food And Nutrition
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• v.24 no.2
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• pp.258-267
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• 2011

14-3-3 is a highly conserved, ubiquitously expressed protein family. It associates with diverse cellular proteins through its specific phosphoserine/phosphothreonine-binding activity and thus contributes to the regulation of crucial cellular processes such as metabolism, signal transduction, cell-cycle control, apoptosis, protein trafficking, transcription and stress responses. This study aims to determine changes in levels of 14-3-3 isoforms and 14-3-3 - associated proteins in Helicobacter pylori(H. pylori)-infected gastric epithelial AGS cells. AGS cells were stimulated with H. pylori(NCTC 11637) at the ratio of 300:1(bacterium:cell). Western blot analysis revealed that 14-3-3 $\sigma$ was elevated at 3 hr after H. pylori treatment. Other isoforms were not significantly affected by H. pylori infection. Using immunoprecipitation to 14-3-3 $\sigma$, followed by proteomic analysis, we found that S phase kinase associated protein isoform 2 bound to 14-3-3 $\sigma$ has increased. In contrast, three proteins (DEAD-box polypeptide 3, heterogeneous nuclear ribonucleoprotein H2 and WD repeat-containing protein isoform 1) bound to 14-3-3 decreased by H. pylori infection. Our results suggest that 14-3-3 may play an important regulatory role in H. pylori-induced signal transduction in gastric epithelial cells.