• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5325-5329
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• 2015

Farnesiferol C is a natural compound with various anti-cancer properties that belongs to the class of sesquiterpene coumarins. However, the low bioavailability of farnesiferol C limits its therapeutic potential. Here, we overcame this problem utilizing dendrosome nano-particles and evaluated the anti-cancer effect of dendrosomal farnesiferol C (DFC) on the AGS gastric cancer cell line. The 3-(4,5-dimethyl-thiazol-2yl)-2,5- diphenyl tetrazolium bromide (MTT) assay and reverse transcriptase-polymerase chain reaction (RT-PCR) were respectively used to detect the anti-proliferative properties of DFC and expression ratio of Bax/Bcl-2 as a hallmark of apoptosis. Compared to the void farnesiferol C (FC), our data showed that DFC significantly suppresses the proliferation of AGS cells in a time- and dose-dependent manner (P<0.01). Also, DFC meaningfully increased the expression ratio of Bax/Bcl-2 in AGS cells (P<0.01). The findings demonstrate that our nano-based formulation of farnesiferol C could be considered as a potential therapeutic agent in cancer targeting.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2425-2430
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• 2015

Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.370-379
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• 2020

Econazole, a potent broad-spectrum antifungal agent and a Ca²⁺ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

• KSBB Journal
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• v.32 no.2
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• pp.83-89
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• 2017

Gamma (${\gamma}$)-oryzanol is a substance abundant in rice, which is widely cultivated in Asian countries. In this study, we evaluated the effect of ${\gamma}$-oryzanol treatment on proliferation and apoptosis of AGS human gastric carcinoma cells. AGS cells were treated with ${\gamma}$-oryzanol for 72 h in a dose dependent manner. Treatment of ${\gamma}$-oryzanol (50, 100, and $200{\mu}g/mL$) resulted in decreased AGS cell proliferation and increased number of cells in the sub-G1 population. Additionally, apoptotic cells were investigated by annexin V staining and mitochondrial membrane potential assays. Our results indicated that ${\gamma}$-oryzanol treatment increased the number of annexin V-positive cells and depolarized cells. This demonstrated that ${\gamma}$-oryzanol is effective for the induction of apoptosis in AGS cells. We next examined the expression of promising anticancer drug target molecules, including PTEN and HSP90. We found that treatment of ${\gamma}$-oryzanol induced the expression of PTEN in AGS cells. Under the same treatment conditions, ${\gamma}$-oryzanol reduced the expression of HSP90 in AGS cells. These results suggest that ${\gamma}$-oryzanol-induced apoptosis was accompanied by changes in regulation of PTEN and HSP90 in AGS cells. Taken together, ${\gamma}$-oryzanol could be used as a functional substance for the prevention of gastric cancer.

• Preventive Nutrition and Food Science
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• v.2 no.2
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• pp.167-173
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• 1997

The inhibitory effects of kale juice on the growh and DNA incorporation of human cancer cells, using HT-29 colon cancer cells, MG-63 osteosarcoma cells, AGS gastric adenocarcinoma cells and K-562 leukemia cells, were studied. The growth of human cancer cells were inhibited in the presence of kale juice (10, 20 nd 40$\mu$l/ml) and the effects were the juice concentration- and incubation time-dependent up to 6 days. When 20$\mu$l/ml of kale juice was added to the media of HT-29, MG-63, AGS and K-562 cancer cells, the cell growth after 6 or 4 days of incubation was retarded by 83~95% of control group. Morphological changes of HT-29 colon cancer cells wre studied under inverted microscope. As the concentration of kale juice increased up to 20$\mu$l/ml, degree of cell aggregation was decreased. Moreover, the DNA incorporation o AGS gastric adenocarcinoma cells and MG-63 osteosarcoma cells which were labeled with [$^3$H] thymidine was significantly reduced after 2 days of incubation at 37$^{\circ}C$ with kale juice. Therefore, we concluded that kale juice strongly decreased the growth of various human cancer cells.

• Microbiology and Biotechnology Letters
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• v.49 no.3
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• pp.283-288
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• 2021

This study investigated the anticancer activity of methanol extract from Platycarya strobilacea leaf in AGS human gastric cancer cells. We determined the cell viability effect of P. strobilacea using MTS assay. Apoptosis induction and cell cycle arrest were confirmed by fluorescein isothiocyanate and propidium iodide staining using cellometer K2. The mRNA expression levels of the Bcl-2 family were confirmed by reverse transcription-polymerase chain reaction. The cell viability was decreased in a dose-dependent manner treated with different concentrations of P. strobilacea. Total, early, and late apoptotic cells were dramatically increased, and the cell cycle was arrested at the sub-G1 phase. The mRNA expressions of Bcl-2 and Bcl-xL were reduced, whereas pro-apoptotic factors, Bax and Bak, were increased in a dose-dependent manner. These results suggested that P. strobilacea leaf extract induced significant apoptotic activity through an intrinsic mitochondria pathway.

• Journal of Life Science
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• v.25 no.8
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• pp.849-860
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• 2015

The anti-cancer activities of Rhus verniciflua Stokes (GC), Ulmus davidiana var. japonica Nakai (UGP) and arsenium sublimatum (SS) extracts, which have been used Oriental medicine therapy for various diseases, were investigated. The treatment of GC, UGP and SS alone, and combined treatment with GC, UGP and SS did not affect the cell viability in the mouse normal cell lines (RAW 264.7 macrophages and C2C12 myoblasts). However, co-treatment with GC, UGP and SS markedly induces apoptosis in human gastric cancer AGS cells, but not in other various cancer cell lines (human lung cancer A549, colon cancer HCT116, liver cancer Hep3B and bladder T24 cells) as evidenced by formation of apoptotic bodies, chromatin condensation, and accumulation of annexin-V positive cells. Co-treatment with GC, UGP and SS effectively induced the expression levels of Fas and Fas ligand, and inhibited the levels IAP family proteins such as XIAP, cIAP-1 and survivin, and anti-apoptotic Bcl-xL proteins compared with treatment with either agent alone. Combined treatment also significantly induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, the cytotoxic effects induced by co-treatment with GC, UGP and SS were significantly attenuated by pan-caspases inhibitor, z-VAD-fmk, indicating an important role for caspases. These results indicated that the caspases were key regulators of apoptosis in response to co-treatment of GC, UGP and SS in human gastric cancer AGS cells and further studies will be needed to identify the active compounds.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.701-709
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• 2006

The Rhus verniciflua Stokes (乾漆-RVS) has been used in traditional East Asia medicine for the therapy of gastritis, stomach cancer, although the mechanism for the biological activity is unclear. In the present study aims to investigate RVS extract contributes to growth inhibitory effect and it's the molecular mechanism on the human gastric cancer cells. AGS (gastric cancer cells) and RIEI (normal cells) were treated to different concentrations and periods of RVS extract $(10{\;}{\sim{{\;}100{\;}ug/mil)$. Growth inhibitory effect was analyzed by measuring FACS study and MTS assay. Cell cycle inhibition was confirmed by measuring CDK2 kinase activity by immunoprecipitation and kinase assay. And apoptosis was confirmed by surveying caspase cascades activation using a pan caspase inhibitor Exposure to RVS extract (50 ug/mll) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces Gl -cell cycle arrest through the regulation of cyclins, the induction of p27kip1, and the decrease CDK2 kinase activity. And upregulated p27kip1 level is caused by protein stability increment by the reduction of S-phase kinase-associated protein 2 (Skp2), a key molecule related with p27kip1 ubiquitination and degradation, and do novo protein synthesis. Besides, 乾漆 extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces Gl -cell cycle arrest via accumulation of p27kip1 and apoptosis in human gastric cancer cells but not in normal cells, therefore we suggest that the extract can be used as a novel class of anti-cancer drugs.

• The Journal of Internal Korean Medicine
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• v.24 no.1
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• pp.134-143
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• 2003

Objectives : We performed this study to understand the molecular basis of the antitumor effect of Saussurea lappa, Pharbitis nil, Plantago asiatica and Taraxacum mongolicum, which have been used for cancer treatment in Korean traditional medicine. Design: We analyzed, the effect of these medicinal herbs on proliferation and apoptosis of tumor cells and its association with gene expression, We performed semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR) analysis of cell cycle- and apoptosis-related genes using a gastric cancer cell line AGS. Results : Cell counting assay and $[^3H]thymidine$ uptake analysis showed that Saussurea lappa and Pharbitis nil strongly inhibit cell proliferation of AGS in a dose-dependent manner. Interestingly, gene espression assay revealed that mRNA espression levels of c-Jun, c-Fos, c-Myc, and Cyclin D1 were markedly decreased by Saussurea lappa and Pharbitis nil. Furthermore, Saussurea lappa was identified to activate expression of the p53 tumor suppressor and its downstream effector $p21^{Wafl}$, which leads to $G_1$ cell cycle arrest and apoptosis. These observations suggest that the anticancer effect of Saussurea lappa and Pharbitis nil might be associated with their regulatory capability of tumor-related gene expression.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.835-842
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• 2016

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays a crucial role in cancer occurrence by promoting cell proliferation and inhibiting apoptosis. In the present study, we evaluated the effect of a PI3K inhibitor, LY294002, on the chemosensitivity of gastric cancer cells to cordycepin, a predominant functional component of the fungus Cordyceps militaris, in AGS human gastric cancer cells and investigated possible underlying cellular mechanisms. Our results revealed that cordycepin inhibited viability of AGS cells in a concentration-dependent manner and induced apoptosis, as determined by apoptotic cell morphologies and fluorescence-activated cell sorting analysis associated with attenuated activation of the PI3K/Akt signaling pathway. Treatment with cordycepin in combination with a subtoxic concentration of LY294002 enhanced cordycepin-induced cytotoxicity and apoptotic potentials in AGS cells. Sensitization of LY294002 to cordycepin-induced apoptosis was accompanied by activation of caspases (caspases-3, -8, and -9) and was concomitant with poly(ADP-ribose) polymerase cleavage. Moreover, LY294002 up-regulated pro-apoptotic Bax and enhanced truncation of Bid in cordycepin-treated AGS cells, which was connected with increased loss of mitochondrial membrane potential and release of cytochrome c from mitochondria to the cytosol. Taken together, these results indicate that inhibition of the PI3K/Akt signaling pathway could augment cordycepin-induced apoptosis in human gastric cancer cells by up-regulating caspase activity through mitochondrial dysfunction.