• 대한약침학회지
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• 제15권3호
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• pp.31-38
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• 2012

Sophorae Radix (SR) plays a role in a number of physiologic and pharmacologic functions in many organs. Objective: The aim of this study was to clarify the potential role for transient receptor potential melastatin 7 (TRPM7) channels in SR-inhibited growth and survival of AGS and MCF-7 cells, the most common human gastric and breast adenocarcinoma cell lines. Methods: The AGS and the MCF-7 cells were treated with varying concentrations of SR. Analyses of the caspase-3 and - 9 activity, the mitochondrial depolarization and the poly (ADPribose) polymerase (PARP) cleavage were conducted to determine if AGS and MCF-7 cell death occured by apoptosis. TRPM7 channel blockers ($Gd^{3+}$ or 2-APB) and small interfering RNA (siRNA) were used in this study to confirm the role of TRPM7 channels. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS and MCF-7 cell growth and survival. Results: The addition of SR to a culture medium inhibited AGS and MCF-7 cell growth and survival. Experimental results showed that the caspase-3 and -9 activity, the mitochondrial depolarization, and the degree of PARP cleavage was increased. TRPM7 channel blockade, either by $Gd^{3+}$ or 2-APB or by suppressing TRPM7 expression with small interfering RNA, blocked the SR-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SR-induced cell death. Conclusions: These findings indicate that SR inhibits the growth and survival of gastric and breast cancer cells due to a blockade of the TRPM7 channel activity. Therefore, TRPM7 channels may play an important role in the survival of patients with gastric and breast cancer.

• 한국식품영양과학회지
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• 제35권2호
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• pp.158-163
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• 2006

유황처리 토양에서 재배한 열무 YR-A와 유황처리 후 복토를 덮어 재배한 열무 YR-B와 이 열무로 김치를 담근김치 A와 김치 B의 pH및 산도와 AGS 인체 위암세포의 성장억제효과에 미치는 영향을 관찰하였다. YR-A로 담근 열무김치 A와 YR-B로 담근 김치 B는 $4\~5$주일째에 적숙기의 pH에 도달하였으며, 이 때 산도는 $0.88\~1.20\%$의 높은 값을 나타내었다. 열무김치 A와 B는 발효가 더욱 진행되어 $6\~8$주일째가 되어도 pH는 4.0이 하로 감소하지 않고 저장성이 길어지는 경향을 나타내었다. 유황처리한 김치 A와 다시 복토를 한 김 치 B는 일반 토양에서 재배한 대조군 김치에 비해 다소 빠른 시일에 적숙기에 도달하였다. 발효초기에는 김치 A가 대조군 김치보다 높은 Leuconostoc속 젖산균 함량을 나타내었으나, Lactobacillus속 젖산균수는 낮은 함량을 나타내었다. 암세포 성장억제효과의 경우, 유황처리 열무 YR-A 즙액 과 VR-B 즙액은 일반토양에서 재배한 YR-Control 즙액에 비해 유의적으로 $70\%$의 높은 암세포 성장억제효과를 나타내었으며, YR-A와 YR-B는 유의적 차이가 없었다. 대조군 김치, 김치 A와 김치 B의 각 즙액은 첨가 농도 $10{\mu}L/assay$에서는 암세포 성장억제효과가 거의 나타나지 않았으나, 첨가 농도 $20{\mu}L/assay$에서 는 약 $74\%$의 AGS 위 암세포에 대한 성장억제효과가 있었으며 이 결과는 열무의 즙액시료 YR-A와 YR-B에서와 비슷한 효과를 나타내는 것으로 보아 열무김치의 발효과정에서는 그 효과가 거의 나타나지 않았음을 알 수 있었다. 열무김치의 메탄올추출물을 이용하여 암세포의 성장억제효과를 관찰한 결과에서도 거의 비슷한 경향을 나타내었다. 따라서 열무 재배시 토양에의 유황처리방법은 열무김치의 발효과정 및 적숙기에서 시원한 맛을 증가시키고 신맛을 감소시켜 유황처리로 재배한 열무김치가 맛 부분에서 다소 우수하다고 할 수 있으나, 유황처리한 열무 YR-A와 다시 복토를 한 열무 YR-B의 산도와 맛에는 별로 차이가 없었다. 또 유황처리토양에서 재배된 열무와 이 열무로 담근 김치즙액의 AGS 암세포 성장 저지효과는 거의 비슷한 수준이었으며, 유황을 첨가하여 재배한 열무의 경우 대조군에 비해 그 효과가 증진되었다. 이 결과에 의하여 유황을 첨가하여 재배한 열무의 암세포의 성장을 저지하는 활성 성분의 증가가 예상되어진다. 본 연구결과로부터 유황처리 열무의 기능성 식품재료로서의 개발가능성을 기대할 수 있으리라 생각된다.

• Journal of Gastric Cancer
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• 제3권2호
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• pp.88-92
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• 2003

Purpose: Mounting evidence suggests that alterations of Akt/protein kinase B (PKB) play an important role in tumorigenesis. Phosphorylated Akt regulates many of the key effector molecules involved in apoptosis, angiogenesis, and cell-cycle progression during tumorigenesis. The expression of phosphorylated Akt has been described in some human malignancies, but not in primary human gastric cancer. The purpose of this study was to explore the expression status of phosphorylated Akt protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of phosphorylated Akt protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the phosphorylated Akt in 42 ($70\%$) of the 60 cancers. Normal gastric mucosal cells showed no or weak expression of phosphorylated Akt protein. Conclusion: Taken together, these results indicate that Akt is frequently activated in gastric adenocarcinoma cells and suggest that phosphorylayed Akt may play a role in the development of human gastric adenocarcinomas.

• 생명과학회지
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• 제20권12호
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• pp.1784-1791
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• 2010

본 연구에서는 AGS 인체 위암세포에서 톳 에탄올 추출물(EHF)의 항침윤성과 tight junctions (TJs)의 tightening과의 관계를 조사하였다. EHF에 의한 AGS 위암세포의 증식억제와 연관된 세포이동성 및 침윤성의 감소는 transepithelial electrical resistance의 증가와 연계된 Js의 tightness 증가와 연관성이 있었다. EHF는 matrix metalloprotease (MMP)-2 및 -9의 활성을 억제하였으며, 이는 MMPs의 mRNA 및 단백질 발현 감소에 의한 것이었으나 tissue inhibitor of metalloproteinase (TIMP)-1 및 -2의 mRNA 발현은 증가시켰다. 또한 EHF는 TJs의 주요 조절인자인 claudin family 단백질들(claudin-1, -3 및 -4)의 발현을 감소시켰으며, insulin like growth factor-1 receptor 단백질은 감소된 반면 thrombospondin-1 및 E-cadherin의 발현은 증가되었다. 본 연구의 결과는 톳 추출물이 암의 전이를 효과적으로 억제하는 효능이 있음을 보여주는 결과이다.

• Applied Microscopy
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• 제32권4호
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• pp.411-419
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• 2002

사람의 위암 조직을 미세구조와 metallothionein (MT)에 대한 면역 조직 및 세포화학적 방법으로 조사하였던 바, 다음과 같은 결과를 얻어냈다. 위암 세포들은 핵 세포질비가 정상세포에 비해 크고, 불규칙한 핵과 이질염색질의 분포가 증가하였으며, 세포질내에서 유리리보솜의 분포가 뚜렷이 증가하였다. 면역 조직 및 세포화학적 방법으로 MT의 발현을 조사하였던 결과, 이 단백질은 위암조직의 암세포에서 반응성이 높게 나타났으며, 주로 핵 부위에 집중되는 경향을 보였으며, 특히 이질염색질과 인 부위에서 면역 금입자들이 주로 분포하는 것으로 관찰되었다. 이러한 결과들은 위암 세포의 미세구조가 미분화세포들이 나타내는 일반적인 특징과 비교되었으며, 위암 세포에서 MT가 증가하는 현상은 이 단백질이 세포질에서 합성되어 핵내로 수송된 후, 세포 증식을 위한 전사과정에 관여할 것임을 시사하는 것이다.

• Animal cells and systems
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• 제15권2호
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• pp.123-130
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• 2011

Transient receptor potential melastatin 7 (TRPM7) channels are novel $Ca^{2+}$-permeable non-selective cation channels that are ubiquitously expressed. Activation of TRPM7 channels has been shown to be involved in the survival of gastric cancer cells. Here we show evidence suggesting that TRPM7 channels play an important role in $Zn^{2+}$- mediated cellular injury. Using a combination of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) methods and cell death assays, we showed that activation of TRPM7 channels augmented $Zn^{2+}$-induced apoptosis of AGS cells, the most common human gastric adenocarcinoma cell line. The $Zn^{2+}$-mediated cytotoxicity was inhibited by the non-specific TRPM7 blockers $Gd^{3+}$ or 2 aminoethoxydiphenyl borate (2-APB) and TRPM7 specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells increased $Zn^{2+}$- induced cell injury. Thus, TRPM7 channels may represent a novel target for physiological disorders where $Zn^{2+}$ toxicity plays an important role.

• 약학회지
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• 제43권3호
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• pp.369-377
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• 1999

A new series of highly water soluble platinum(II) complexes {Pt(II)[1,3-bis(phenylthio) propane](trans- -1,2-diaminocyclohexane) (PC-1) and Pt(II)[1,3-bis-(phenythio)propane] cis-1,2-diaminocyclohexane(PC-2)} were synthesized, and characterized by their elemental analysis and by various spectroscopic techniques[infrared(IR), 13C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II) complexes was tested against P-388 and L-1210 mouse lymphocytic leukemia cell lines, PC-14 / P, PC-14/ADM and PC-14 / CDDP human pulmonary adenocarcinima, DU-145 human prostate carcinoma, HT-1376 human bladder carcinoma, ZR-75-1 human breast carcinoma, MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 showed active against L-1210, P-388 leukemia, human lung, stomach, prostate, bladder and breast cancer cell lines, and the antitumor activity of these compounds were comparable or superior to those of PC-2 and displatin. The nephrotoxicities of PC-1 and PC-2 were found quite less than that of cisplatin using MTT and [3H] thymidine uptake in rabbit proximal tubule cells and human kidney cortical cells. Based on these results, this novel platinum (II) complex compound (PC-1) represents a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.190-194
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• 2007

Gastric adenocarcinoma (GA) is a major tumor type of gastric cancers and subdivides into several different tumors such as papillary, tubular mucinous, signet-ring cell and adenosquamous carcinoma according to histopatholigical determination. In other hand, GA is also subdivided into intestinal and diffuse type of adenocarcinoma by the Lauren?fs classification. In this study, we have examined differential gene expression pattern analysis of three histologically different GAs of 24 samples by using DNA microarray containing approximately 19000 genetic elements. The hierarchical clustering analysis of 24 gastric adenocarcinomas (12 of intestinal type, 7 of diffuse type and 5 of mixed type) resulted in two major subgroup on dendrogram, and two subgroups included most of intestinal and diffused type of GAs respectively. Supervised analysis of 19 intestinal and diffuse type GAs by using Wilcoxon rank T-test (P<0.01) resulted in 100 outlier genes which exactly separated intestinal and diffuse type of GA by differential gene expression. In conclusion, genome-wide analysis of gene expression of GAs suggested that GAs may subclassify as intestinal and diffused type of GA by their characteristic molecular expression. Our results also provide large-scale genetic elements which reflect molecular differences of intestinal and diffuse type of GAs, and this may facilitate to understand different molecular carcinogenesis of gastric cancer.

• Journal of Applied Biological Chemistry
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• 제59권3호
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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.

• 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.