• Journal of Life Science
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• v.21 no.2
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• pp.286-291
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• 2011

Hypoxia is a common condition found in a wide range of solid tumors and is often associated with metastasis and poor clinical outcomes. In the present study, we found that HIF-$1{\alpha}$ was induced by cobalt chloride (500 ${\mu}M$) treatment on human lung cancer cells, A549 and H460, for 24 hr. However, cobalt chloride (500 ${\mu}M$) did not affect cell proliferation of A549 and H460 in 48 hr. Cobalt chloride (500 ${\mu}M$) additionally induced epithelial-to-mesenchymal-like transition (EMT) such as reduced E-cadherin expression and increased ${\alpha}$-SMA expression. These results were confirmed by immunofluorecence experiment in H460 cells. E-cadherin was localized on the outer cell membrane. However, when the cells were treated with 500 ${\mu}M$ cobalt chloride for 24 hr, diffuse E-cadherin staining was observed, characteristic of a migratory mesenchymal phenotype. We also found that cobalt chloride induced integrin ${\beta}3$ expression and FAK phosphorylation in human lung cancer cells using western blotting and FACS anlaysis. Our data suggest that integrin ${\beta}3$-induced FAK phosphorylation may be developed into target molecules for blocking tumor metastasis.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.286-291
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• 1996

Phenolic compounds are prevalent as toxins or environmental pollutants, but they are also widely used as drugs for various purpose including anticancer agent. A novel biphenolic compound, bis(2-hydroxy-3-tert-butyl-5-methylphenyl)methane (GERI-BPO02-A) was isolated from the fermentation broth of Aspergillus fumigatus F93 previously, and it has revealed cytotoxicity against human solid tumor cells. Its effective doses that cause 50% inhibition of cell growth in vitro against non-small cell lung cancer cell A549, ovarian cancer cell SK-OV-3, skin cancer cell SK-MEL-2 and central nerve system cancer cell XF498 were 8.24, 10.60, 8.83, $9.85\mug/ml$ respectively. GERI-BPO02-A has also revealed cytotoxicity against P-glycoproteinexpressed human colon cancer cell HCT15 and its multidrug-resistant subline HCT15/CL02, and its cytotoxicity was not affected by P-glycoprotein. We have also tested cytotoxicities of structurally related compounds of GERI-BPO02-A such as diphenylmethane, 1,1-bis(3,4dimethylphenyl)ethane, 2,2-diphenylpropane, 2-benzylpyridine, 3-benzylpyridine, $4,4^I-di-tert-butylphenyl$, bibenzyl, $2,2^I-dimethylbibenzyl$, cis-stilbene, trans-stilbene, 3-tert-butyl-4-hydroxy-5-methylphenyisulfide, sulfadiazine and sulfisomidine for studying of structure and activity relationship, and from these data we could suppose that hydroxyl group of GERI-BPO02A conducted important role in its cytotoxicity.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.336-344
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• 2004

Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

• Journal of the Korean Applied Science and Technology
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• v.33 no.1
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• pp.41-50
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• 2016

In this study, the extracts from the leaves of Rhaphiolepis indica(R. indica) and Quercus salicina(Q. salicina) confirmed antioxidative effects. The antioxidative and cytotoxic effects of the two extracts were analyzed according to varied concentrations and time. The extracts of R. indica and Q. salicina showed dose-dependent DPPH radical scavenging activities. The extracts of R. indica and Q. salicina at concentrations of 5 mg/mL showed DPPH radical scavenging activities at 89.93 and 92.41%. Therefore, Q. salicina were confirmed to have higher antioxidative effects than R. indica. Total phenolic contents were 65.20 mg GAE/g for R. indica and 85.20 mg GAE/g for Q. salicina. The result that Q. salicina have higher total phenolic contents than R. indica suggested a correlation between total phenolic contents and DPPH radical scavenging activity. The cell protective effects of HepG2 and A549 cells under oxidative stress, both the extracts showed relatively low cell protective effects at around 10%. The Cytotoxic effects of A549 Cells did not show cytotoxicity at concentrations of $100{\mu}g/mL$ or below. The results of this study are likely to be used as basic data to develop antioxidants using the extract of R. indica and Q. salicina.

• Korean Journal of Medicinal Crop Science
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• v.8 no.1
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• pp.21-28
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• 2000

The biological activities of water, ethanol and 50% ethanol extracts from Acanthopanax root bark were compared. 94% of Hep3B cell growth was inhibited by adding 1.0g/L of 50% ethanol extracts from A. senticosus root bark. It was also showed that above 90% of A549 cell growth was inhibited by adding 1.0g/L of 50% ethanol extracts. The 50% ethanol extracts of A. sessiliflorum root bark showed that the extracts selectivity were from 1.5 to 3.4 by adding all samples. For screening immunomodulating activities, Jurkat(T-cell) was showed that the cell growth and viability were more increased and activited 275% by adding the 50% ethanol extracts from A. senticosus root bark. The result of anti-mutagenicity of 50% ethanol extracts of A. senticosus root bark was most effective than any other samples. The enhancement of glutathione-S-transferase activity was increased 241% by adding 1.0g/L 1 : 1 extracts of A. senticosus root bark. 72% of oxidation was inhibited by adding 1.0g/L of 50% ethanol extracts from A. senticosus root bark.

• Korean Journal of Pharmacognosy
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• v.37 no.3
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• pp.206-211
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• 2006

The methanol extract from seed of Myristica fragrans (Myristicaceae) demonstrated a potent inhibition on the pro-liferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon) in vitro. By the continuous effort to purify the active components responsible far the anti-proliferative effect on tumor cell lines, we have isolated eleven kinds of lignan components, i. e., safrole (1), machilin A (2), licarin B (3), macelignan (4), mere-dihydroguaiaretic acid (5), mγnstargenol A (6), methoxyeugenol (7), machilin F (8), licarin A (9), nectandrin B (10), and 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propan-1-ol (11) together with a novel furan fatty acid, (E)-3-(3-methyl-5-pentylfuran-2-yl) acrylic acid (12) from seed extract of M. fragrans. Chemical structures of the isolated components (1-12) were established bγ the aid of NMR spectroscopic analyses, i. e., COSY HMQC and HMBC. Each of the Isolates demonstrated a potent inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OY-3 (ovary), SK-MEL-2 (melanoma) and HCT-15 (colon) in vitro.

• Journal of Microbiology
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• v.37 no.2
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• pp.111-116
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• 1999

Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is known to act as a signal transducer that connects TNFR2 to its downstream effector functions such as proliferation of thymocytes, regulation of gene expression, and cell death. TRAF2 consists of largely two domains, the N-terminal half that contains a signal-emanating region and the C-terminal half that is responsible for binding to the intracellular region of TNFR2. In this study, we examined the possible roles of TRAF2 in granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression and cell death. A truncated mutant of TRAF2 ( 2-263) that contains only a C-terminal half was generated, and transiently transfected to the A549 cell, a human lung cancer cell line, and L929 cell, a murine TNF-sensitive cell line. GM-CSF mRNA was induced in untransfected A540 cells both in dose- and time-dependent manner upon the exposure of TNF. However, neither the full length TRAF2 nor the mutant altered GM-CSF mRNA production regardless of the presence or absence of TNF. Furthermore, neither TRAF2 versions significantly changed the cytotoxic effect of TNF on L929 cells. These data suggest that TRAF2 may not be involved in the signal transduction pathway for GM-CSF gene induction and cell death mediated by TNF.

• Proceedings of the Korean Society of Postharvest Science and Technology of Agricultural Products Conference
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• 2003.10a
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• pp.148.1-148
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• 2003

버섯은 균사체와 자실체를 가진 고등균류로서 옛날부터 식용은 물론 약용으로 많이 사용되어 왔으며 부작용이 없는 저칼로리 식품으로서, 영양적인 측면과 의약품으로서의 효능을 가진 식품으로 인식되어 소비량이 날로 증가하는 추세이다. 버섯은 항균자용, 항암작용, 면역증강작용, 혈압강하 효과 및 혈중 콜레스테롤합성 억제효과 등의 다양한 생리활성을 나타내고 있어 국내에서도 버섯의 균사체 배양이 활기를 띄고 있다. 본 연구에서는 5종류의 버섯(아가리쿠스, 상황, 노루궁뎅이, 운지, 동충하초)의 균사체 배양원액을 10%, 30%, 50%, 100% 함유한 음료로서 전자공여능, 아질산염소거능, MDA cell과 A549 cell에 대한 암세포 증식억제 작용을 조사하였다. 5종류의 버섯 균사체 음료의 전자공여능은 발효원액을 30% 함유한 경우에 72∼89%였으며 100% 원액의 경우는 87∼93%의 탁월한 항산화능을 나타내었다. 균사체 음료의 아질산염 소거능은 노루궁뎅이버섯이 가장 높아서 균사체 원액은 73%, 112 희석액은 51%였으며 다음은 동충하초의 균사체 원액이 52%를 나타내었고 나머지 3종류의 버섯 균사체는 28∼36%의 아질산염소거능을 나타내었다. 균사체 발효음료 원액은 MBA cell에 대하여 5종류의 버섯 모두에서 82∼85%의 높은 암세포 증식억제작용을 나타내었고 동충하초는 1/2 희석액에서도 80%이상의 증식억제활성을 나타내었다. 균사체 발효음료 원액의 A549 cell에 대한 증식억제능은 동충하초 발효원액이 68%, 상황 발효원액이 50%로서 MDA cell에 대한 증식억제효과 보다는 효능이 낮은 편이었다. 전체적으로 5종류의 버섯 균사체 발효음료는 항산화작용, 아질산염소거능, 항암활성이 우수한 기능성 음료로 활용될 수 있을 것으로 생각된다.적으로 평가하는데 적합하나 아직 국내에선 X-선을 이용한 가공용 감자의 내부 결함특성에 대한 연구는 이뤄지지 않고 있다. 이에 본 연구에서는 가공용 감자의 내부결함 특성중 하나인 내부동공의 X-선에 의한 특성을 본 연구소에 있는 X-선 발생장비로 측정해 보고 비파괴적인 방법으로 실시간 가능성을 시험하였다. 감자는 수원 농산물 도매시장에서 2003년산 가공용 감자 (품종:선농)를 구매하여 사용하였다. 감자내 내부동공은 35 ∼ 40 kV와 5.25 mA값으로 발생된 X-선에 의해 잘 검출되는 것으로 나타나, 현장에서 충분히 활용가능 할 것으로 판단되었다. 금후, 실시간으로 내부동공을 검출할 수 있는 시스템을 개발할 계획이다.정한 결과 메탄올에서는 5% 농도차이가 그 추출효율에 유의적인 영향을 주지 않는 것으로 나타났다. 에탄올에서는 40%에서 가장 높은 함량이 측정되었고 아세톤에서는 50%에서 측정되었다. 따라서 시료의 상태와 상관없이 배 과피의 페놀성물질 추출용매로는 40∼70%의 함수 아세톤이 적합한 것으로 사료된다.en delicious는 상온에서60일 동안 보관하였을 경우, 사과표피의 색도 변화를 현저히 지연시킴을 확인하였다. 또한 control과 비교하여 성공적으로 사과에 코팅하였으며, 상온에서 보관하여을 때 사과의 품질을 30일 이상 연장하는 효과를 관찰하였다. 이들 결과로부터 대두단백질 필름이 과일 등의 포장제로서 이용할 가능성을 확인하였다.로 [-wh] 겹의문사는 복수 의미를 지닐 수 없 다. 그러면 단수 의미는 어떻게 생성되는가\ulcorner 본 논문에서는 표면적 형태에도 불구하고 [-wh]의미의 겹의문사는 병렬적 관계의 합성어가 아니라 내부구조를 지니지 않은 단순한 단어(minimal $X^{0}$ elements

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1271-1284
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majority of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host. In the previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF, and the probability was shown that the acquired resistance to TNF might be associated with synthesis of some protective protein. Understanding the mechanisms of TNF-resistance in TNF-$\alpha$ cDNA transfected cancer cells would be an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate whether the levels of TNF receptor mRNA expression and soluble TNF receptor release from cancer cells are changed after TNF-$\alpha$ cDNA transfection. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164(murine fibrosarcoma cell line), NCI-H2058(human mesothelioma cell line), A549(human non-small cell lung cancer cell line), ME180(human cervix cancer cell line) cells using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, EUSA, MTT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and evaluated the TNF receptor mRNA expression with Northern blot analysis and soluble TNF receptor release with EUSA. Results : The TNF receptor mRNA expressions of parental cells and genetically modified cells were not significantly different. The soluble TNF receptor levels of media from genetically modified cells were lower than those from parental cells. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the TNF receptor and the soluble TNF receptor expression.

• Korean Journal of Food Science and Technology
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• v.51 no.5
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• pp.503-508
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• 2019

To evaluate the protective effect of Ecklonia cava on ultra-fine dust ($PM_{2.5}$)-induced cytotoxicity, we investigated the in vitro antioxidant activity and cell viability after exposure to $PM_{2.5}$. E. cava was extracted using water and 80% ethanol, and antioxidant activity was determined using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS)/2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and lipid peroxidation inhibition assays. The 80% ethanol extract showed relatively higher antioxidant activity than the water extract. The cell protective effects were determined by measuring the intracellular reactive oxygen species (ROS) content and viability of nasal epithelial (RPMI-2650), lung epithelial (A549), and brain neuroblastoma (MC-IXC) cells. Results showed that the 80% ethanol extract inhibited ROS production more than the water extract. In contrast, both extracts showed similar effects on cell viability in the $PM_{2.5}$-induced cell death assay. Thus, Ecklonia cava may act as an effective resource for preventing $PM_{2.5}$-induced cytotoxicity in nasal, lung, and brain cells.