• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5189-5193
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• 2016

Objective: Dorema glabrum Fisch. & C.A. Mey is a perennial plant that has several curative properties. Anti-proliferative activity of seeds of this plant has been demonstrated in a mouse fibrosarcoma cell line. The aim of the present study was to evaluate cytotoxicity of D. glabrum root extracts in a human gastric adenocarcinoma (AGS) cell line and explore mechanisms of apoptosis induction, cell cycle arrest and altered gene expression in cancer cells. Materials and Methods: The MTT assay was used to evaluate IC50 values, EB/AO staining to analyze the mode of cell death, and flow cytometry to assess the cell cycle. Quantitative real-time polymerase chain reaction (qRT-PCR) amplification was performed with apoptosis and cell cycle-related gene primers, for cyclin D1, c-myc, survivin, VEGF, Bcl-2, Bax, and caspase-3 to determine alteration of gene expression. Results: Our results showed that n-hexane and chloroform extracts had greatest toxic effects on gastric cancer cells with IC50 values of $6.4{\mu}g/ml$ and $4.6{\mu}g/ml$, respectively, after 72 h. Cell cycle analysis revealed that the population of treated cells in the G1 phase was increased in comparison to controls. Cellular morphological changes indicated induction of apoptosis. In addition, mRNA expression levels of Bax and caspase-3 were increased, and of bcl-2 survivin, VEGF, c-myc and cyclin D1 were decreased. Conclusion: Our study results suggest that D. glabrum has cytotoxic effects on AGS cells, characterized by enhanced apoptosis, reduced cell viability and arrest of cell cycling.

• Molecules and Cells
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• 제28권6호
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• pp.521-527
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• 2009

Previously, we have reported tissue- and stage-specific expression of miR-372 in human embryonic stem cells and so far, not many reports speculate the function of this microRNA (miRNA). In this study, we screened various human cancer cell lines including gastric cancer cell lines and found first time that miR-372 is expressed only in AGS human gastric adenocarcinoma cell line. Inhibition of miR-372 using antisense miR-372 oligonucleotide (AS-miR-372) suppressed proliferation, arrested the cell cycle at G2/M phase, and increased apoptosis of AGS cells. Furthermore, AS-miR-372 treatment increased expression of LATS2, while over-expression of miR-372 decreased luciferase reporter activity driven by the 3' untranslated region (3' UTR) of LATS2 mRNA. Over-expression of LATS2 induced changes in AGS cells similar to those in AGS cells treated with AS-miR-372. Taken together, these findings demonstrate an oncogenic role for miR-372 in controlling cell growth, cell cycle, and apoptosis through down-regulation of a tumor suppressor gene, LATS2.

• Biomolecules & Therapeutics
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• 제8권3호
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• pp.228-234
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• 2000

We have synthesized a novel platinum(II) coordination complex containing trans-ι-1,2-diaminocy-clohexane (DACH) as a carrier ligand and 1,2-dichloroethane (DCE) as a leaving group. A new series of [Pt(trans-ι-DACH)(DCE)](PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocar-cinoma cells and normal primary cultured kidney cells. The new platinum complex has demonstrated high efficacy in the cytotoxicity against MKN-45/P, MKN-45/ADM and MKN-45/CDDP cell-lines. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined by MTT assay, the [$^3H$]-thymidine uptake arid glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new, clinically available anticancer chemotherapeutic agents.

• 약학회지
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• 제44권5호
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• pp.399-405
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• 2000

We have synthesized a novel platinum (II) coordination complex containing trans-ι-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis (diphenylphosphino)ethane (DPPE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt (trans-ι-DACH) (DPPE)].2NO$_3$(PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against MKN-45/S, MKN-45/ADR and MKN-45/CDDP cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells, and human renal cortical tissues, determined using the MTT assaying technique, the ($^3$H)-thymidine uptake and the glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum (II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.

• 대한약침학회지
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• 제16권2호
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• pp.55-61
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• 2013

Objective: Ulmi Pumilae Cortex (UPC) is a deciduous tree with uneven pinnate leaves and is classified as a subfamily of Ulmuceae and contains many pharmacologically active constituents. The aim of this study was to investigate the effects of UPC on the growth and survival of AGS cells, the most common human gastric adenocarcinoma cell lines. Methods: The AGS cells were treated with varying concentrations of UPC. Analyses of the sub G1, caspase-3 activity, and mitochondrial depolarization were conducted to determine whether AGS cell death occured by apoptosis. Furthermore, to identify the role of the transient receptor potential melastatin (TRPM) 7 channels in AGS cell growth and survival, we used human embryonic kidney (HEK) 293 cells overexpressed with TRPM7 channels. Results: The addition of UPC to a culture medium inhibited AGS cell growth and survival. Experimental results showed that the sub G1, caspase-3 activity, and mitochondrial depolarization were increased. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated UPC-induced cell death. Conclusion: These findings indicate that UPC inhibits the growth and survival of gastric cancer cells due to a blockade of the TRPM7 channel activity. Therefore, UPC is a potential drug for treatment of gastric cancer, and TRPM7 channels may play an important role in survival in cases of gastric cancer.

• 대한약침학회지
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• 제16권3호
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• pp.39-45
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• 2013

Objectives: Buxus Microphylla var. Koreana Nakai Extract (BMKNE) is used as a folk remedy for malaria and veneral disease. In the present study, we investigated the effects of BMKNE in the growth and the survival of AGS cells, the most common human gastric adenocarcinoma cell lines. Methods: The AGS cells were treated with varying concentrations of BMKNE. Analyses of the sub G1 peak, the caspase-3 and -9 activities, and the mitochondrial depolarization were conducted to determine whether AGS cell death occured by apoptosis. Also, to identify the role of transient receptor potential melastatin (TRPM) 7 channels in AGS cell growth and survival, we used human embryonic kidney (HEK) 293 cells overexpressed with TRPM7 channels. Results: Experimental results showed that the sub G1 peak, the caspase-3 and -9 activities, and the mitochondrial depolarization were increased. Therefore, BMKNE was found to induce the apoptosis of these cells, and this apoptosis was inhibited by SB203580 (a p38 mitogen-activated protein kinase (MAPK) inhibitor), and by a c-jun NH2-terminal kinase (JNK) II inhibitor. Furthermore, BMKNE inhibited TRPM7 currents and TRPM7 channel over-expressions in HEK 293 cells, exacerbating BMKNE-induced cell death. Conclusions: These findings indicate that BMKNE inhibits the growth and the survival of gastric cancer cells due to a blockade of the TRPM7 channel's activity and MAPK signaling. Therefore, BMKNE is a potential drug for treatment of gastric cancer, and both the TRPM7 channel and MAPK signaling may play an important role in survival in gastric cancer cells.

• Journal of Digestive Cancer Research
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• 제1권1호
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• pp.24-28
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• 2013

위암은 최근 50년간 5년 생존율에 있어서 미약하게만 상승되었다. 이에 따라 위암에 대한 분자생물학적 치료에 대한 여러 연구가 진행되고 있다. 이에 진행성, 전이성 위암에서의 분자생물학적 치료에 대해 살펴보고자 한다. 위암의 분자생물학적 치료의 타켓으로는 EGFR (Epidermal growth factor receptor), HER(Human epidermal growth factor receptor), VEGF (Vascular endothelial growth factor receptor)를 들 수 있다. 대표적으로 분자생물학적 치료 중 trastuzumab은 HER2과발현 환자에게 유용하게 사용될 수 있어, 기존 항암화학요법에 복합투여해 볼 수 있다. Trastuzumab와 그 밖의 여러 분자생물학적 제재에 대해 본 연구에서 살펴보고자 한다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2004년도 춘계 총회 및 학술대회
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• pp.63-63
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• 2004

• Preventive Nutrition and Food Science
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• 제21권1호
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• pp.31-37
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• 2016

Opuntia humifusa (OHF) has been used as a nutraceutical source for the prevention of chronic diseases. In the present study, the inhibitory effects of ethyl acetate extracts of OHF on the proliferation of AGS human gastric cancer cells and the mode of action were investigated. To elucidate the antiproliferative mechanisms of OHF in cancer cells, the expression of genes related to apoptosis and cell cycle arrest were determined with real-time PCR and western blot. The cytotoxic effect of OHF on AGS cells was observed in a dose-dependent manner. Exposure to OHF ($100{\mu}g/mL$) significantly induced (P<0.05) the G1 phase cell cycle arrest. Additionally, the apoptotic cell population was greater (P<0.05) in OHF ($200{\mu}g/mL$) treated AGS cells when compared to the control. The expression of genes associated with cell cycle progression (Cdk4, Cdk2, and cyclin E) was significantly downregulated (P<0.05) by the OHF treatment. Moreover, the expression of Bax and caspase-3 in OHF treated cells was higher (P<0.05) than in the control. These findings suggest that OHF induces the G1 phase cell cycle arrest and activation of mitochondria-mediated apoptosis pathway in AGS human gastric cancer cells.

• Preventive Nutrition and Food Science
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• 제8권1호
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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.