• Preventive Nutrition and Food Science
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• v.10 no.4
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• pp.349-352
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• 2005

The growth inhibitory effect of wheat grain, fermented wheat grain products, red pepper powder and kochujang was examined in AGS human gastric adenocarcinoma cells. The kochujang samples were prepared by mixing red pepper powder and each fermented wheat grain products, such as first fermented wheat grain (FFWG), second fermented wheat grain (SFWG) and final fermented wheat grain (FiFWG). The methanol extract of FiFWG showed the highest growth inhibitory effects. In order to investigate the effects of fermented wheat grain products at each stage of fermentation on anticancer activity, the kochujang prepared with red pepper powder and each of FFWG, SFWG and FiFWG were fermented until reaching pH 5.1. The kochujang adjusted to pH 5.1 by fermentation increased the growth inhibitory effect; however, the kochujang prepared with FiFWG showed the highest effect. Increased fermentation time increased the growth inhibitory effect of kochujang when prepared with FiFWG. These results suggested that the anticancer effect of the kochujang on the gastric cancer cells was affected by the fermentation periods of the wheat grains. The well-fermented end products of the wheat grains seem to be one of the major components that showed anticancer activity of kochujang.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.216-221
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• 2019

The c-Met protein is a receptor tyrosine kinase involved in cell growth, proliferation, survival, and angiogenesis of several human tumors. Overexpression of c-Met has been found in gastric cancers and correlated with a poor prognosis. Indirubin is the active component of Danggui Longhui Wan, which is a traditional Chinese antileukemic recipe. In the present study, we tested the anti-cancer effects of an indirubin derivative, LDD-1937, on human gastric cancer cells SNU-638. When we performed the in vitro kinase assay against the c-Met activity, LDD-1937 inhibited the activity of c-Met. This result was confirmed by immunoblot and immunofluorescence of phosphorylated c-Met. Immunoblot analysis showed that LDD-1937 decreased the expression of the Erk1/2, STAT3, STAT5, and Akt, downstream proteins of c-Met. In addition, LDD-1937 reduced the cell viability and suppressed colony formation and migration of SNU-638 cells. Furthermore, LDD-1937 induced $G_2/M$ phase arrest in the SNU-638 cells by decreasing the expression levels of cyclin B1 and CDC2. Cleaved-PARP, an apoptosis-related protein, was up-regulated in cells treated with LDD-1937. Overall, this study suggests that LDD-1937 may be a novel small-molecule with therapeutic potential for selectively inhibiting c-Met and c-Met downstream pathways in human gastric cancers overexpressing c-Met.

• Journal of Food Hygiene and Safety
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• v.36 no.1
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• pp.100-104
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• 2021

trans-Cinnamaldehyde (TCA), as one of the active ingredients in cinnamon, has been reported to have antiviral, antibacterial and antifungal effects as well as anti-cancer effects in several cancer cell lines. However, reports of TCA in gastric cancer are rare, and its mechanism is unclear. In this study, we investigated the anti-proliferative effect of TCA and its mechanism in gastric cancer AGS cells. TCA dose-dependently inhibited the cell viability of AGS cells. Our results suggested that TCA induces apoptosis through changes in cell morphology. To elucidate its mechanism, we investigated the expression level of apoptosis-related proteins. TCA induced the expression of p53 and Bax proteins, and then increased the cleaved caspase 9 and cleaved PARP. These results indicated that TCA triggers apoptosis via p53 pathway in AGS cells. Our results suggested that TCA might be a new anticancer drug candidate for gastric cancer.

• Journal of Web Engineering
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• v.14 no.15
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• pp.3206-3218
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• 2022

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and triggers various stomach diseases. H. pylori induces reactive oxygen species (ROS) production and DNA damage. The heterodimeric Ku70/Ku80 protein plays an essential role in the repair of DNA double-strand breaks (DSB). Oxidative stress stimulate apoptosis and DNA damage that can be repaired by Ku70/80. However, excessive reactive oxygen species (ROS) can cause Ku protein degradation, resulting in DNA fragmentation and apoptosis. α-lipoic acid (α-LA), which is found in organ meats such as liver and heart, spinach, broccoli, and potatoes, quenches free radicals, chelates metal ions, and reduces intracellular DNA damage induced by oxidative stress. Here, we investigated whether H. pylori decreases Ku70/80 and induces apoptosis, and whether α-LA inhibits changes induced by H. pylori. We analyzed ROS, DNA damage markers (γ-H2AX, DNA fragmentation), levels of Ku70/80, Ku-DNA binding activity, Ku80 ubiquitination, apoptosis indices (Bcl-2, Bax, apoptosis-inducing factor (AIF), and caspase-3), and viability in a human gastric epithelial adenocarcinoma cell line (AGS). H. pylori increased ROS, DNA damage markers, Ku80 ubiquitination, and consequently induced apoptosis. It also decreased nuclear Ku70/80 levels and Ku-DNA-binding activity; increased Bax expression, caspase-3 cleavage, and truncated AIF; but decreased Bcl-2 expression. These H. pylori-induced alterations were inhibited by α-LA. The antioxidant N-acetylcysteine and proteasome inhibitor MG-132 suppressed H. pylori-induced cell death and decreased nuclear Ku70/80 levels. The results show that oxidative stress induced Ku70/80 degradation via the ubiquitin-proteasome system, leading to its nuclear loss and apoptosis in H. pylori-infected cells. In conclusion, α-LA inhibited apoptosis induced by H. pylori by reducing ROS levels and suppressing the loss of Ku70/80 proteins in AGS cells.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.35-43
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• 2007

Objectives : The purpose of this study was to investigate the effect of Bo-du-san (BOS) on apoptosis in human gastric cancer cells, SNU-l cells. BOS, a drug preparation consisting of two herbs, that is, Crotonis Fructus (Strychni ignatii Semen, bodu in Korean) and Glycyrrhizae Radix (Glycyrrhizae uralensis FISCH, Gamcho in Korean). Methodss : In this study, methanol extract of BOS was examined for cytotoxic activity on human gastric cancer cells, SNU-1 cells, using XTT assay, with an IC50 value was 0.7 mg/ml and 0.3 mg/ml at 24 hrs and 48 hrs, respectively. Apoptosis induction by BDS in SNU-l cells was verified by the induction of DNA fragmentation, cleavage of poly ADP-ribose polymerase (PARP), and activation of caspase-3, -8 and -9. Inhibitors of caspase-3, -8 and -9 (Ac-DEVD-CHO, Z-IETD-FMK and Z-LEHD-FMK) efficiently blocked BOS-induced cell death of SNU-l. Resultss : BOS-induced cell death was via caspase dependent apoptosis. Moreover, treatment of BOS result in the decrease the G1/S cycle regulation proteins (cyclin D1 and E) expression and increase CDK inhibitor proteins (p21 and p27) expression, and increase apoptotic protein, p53 expression. Thus, BOS induces apoptosis in SNU-1 cells via cell cycle arrested in G1 phase. Conclusions : These results indicated that BOS has some potential for use as an anti-cancer agent.

• 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.

• Molecules and Cells
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• v.20 no.3
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• pp.435-441
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• 2005

Classical transient receptor potential channels (TRPCs) are thought to be candidates for the nonselective cation channels (NSCCs) involved in pacemaker activity and its neuromodulation in murine stomach smooth muscle. We aimed to determine the role of TRPC4 in the formation of NSCCs and in the generation of slow waves. At a holding potential of -60 mV, $50{\mu}M$ carbachol (CCh) induced $I_{NSCC}$ of amplitude [$500.8{\pm}161.8pA$ (n = 8)] at -60 mV in mouse gastric smooth muscle cells. We investigated the effects of commercially available antibodies to TRPC4 on recombinant TRPC4 expressed in HEK cells and CCh-induced NSCCs in gastric smooth muscle cells. TRPC4 currents in HEK cells were reduced from $1525.6{\pm}414.4pA$ (n = 8) to $146.4{\pm}83.3pA$ (n = 10) by anti-TRPC4 antibody and $I_{NSCC}$ amplitudes were reduced from $230.9{\pm}36.3pA$ (n = 15) to $49.8{\pm}11.8pA$ (n = 9). Furthermore, $I_{NSCC}$ in the gastric smooth muscle cells of TRPC4 knockout mice was only $34.4{\pm}10.4pA$ (n = 8) at -60 mV. However, slow waves were still present in the knockout mice. Our data suggest that TRPC4 is an essential component of the NSCC activated by muscarinic stimulation in the murine stomach.

• Preventive Nutrition and Food Science
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• v.8 no.1
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• pp.54-60
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• 2003

To develop a functional chungkookjang; the anticancer effects of chungkookjangs prepared with different varieties of soybeans, starters, fermentation periods and seasoning additive ratios; were studied against AGS human gastric adenocarcinoma cells using the MTT assay, at different stages chungkookjang processing. The chungkookjang samples exerted different antiproliferative effects according to the variety of soybeans used. The chungkookjangs manufactured with soybean var. manrikong exhibited the highest cytotoxicity against AGS human cancer cells. The chungkookjangs fermented with rice straw and B. licheniformis strongly inhibited the growth of the AGS human cancer cells. All fermented chungkookjangs had a strong inhibitory effect on the growth of the cancer cells; however, the non-fermented soybean (chungkookjang) showed a low inhibition rate. The fermented chungkookjangs mixed with red pepper powder (RPP) and garlic exhibited strong antiproliferative effect against the cancer cells, and chungkookjang prepaved with 1.1 % RPP and 1.1 % garlic showed the highest cytotoxicity against the cancer cells. The functional chungkookjang fermented with soybean variety of manrikong and B. licheniformis for 3 days at 4$0^{\circ}C$ and then mixed with 7.9% salt, 1.l% RPP and 1.1% garlic, exhibited a higher antiproliferative effect than the chungkookjangs prepared by traditional or modified methods, according to the MTT assay. The functional chungkookjang exhibited a similar anticancer effect to the traditional doenjang. These results indicate that the fermentation period and the ratio of seasoning additives, as well as the variety of soybeans and starter cultures may affect the degree of the anticancer effect of chungkookjang.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.135-135
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• 2000

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3523-3525
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• 2015

Gastric cancer is the second most common cause of cancer death worldwide. Environmental as well as genetic factors have been shown to be involved in its genesis. Among genetic factors, loss of function of a tumor suppressive gene named promyelocytic leukemia (PML) has been demonstrated in gastric cancer. In order to cast light in the mechanism by which PML protein is under-expressed in gastric cancer cells, we analyzed all exons and intron-exon boundaries of PML gene in 50 formalin-fixed paraffin-embedded tissue blocks from gastric carcinoma tumors by means of PCR-SSCP and CSGE, with direct sequencing of abnormally shifted bands. We found a novel sequence variant of unknown significance localized in intron 5 in 3 samples (c.1398+84delA). We did not detect any deleterious mutations of the PML gene. This study shows that PML mutations may not contribute to gastric adenocarcinoma development. Post-translational modifications or protein degradation might be mechanisms by which PML is not expressed in gastric tumors.