• Title/Summary/Keyword: A549 cell

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Thrombin inhibits HMGB1-mediated proinflammatory signaling responses when endothelial protein C receptor is occupied by its natural ligand

  • Bae, Jong-Sup;Rezaie, Alireza R.
    • BMB Reports
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    • v.46 no.11
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    • pp.544-549
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    • 2013
  • High mobility group box 1 (HMGB1) is involved in the pathogenesis of vascular diseases. Unlike activated protein C (APC), the activation of PAR-1 by thrombin is known to elicit proinflammatory responses. To determine whether the occupancy of EPCR by the Gla-domain of APC is responsible for the PAR-1-dependent antiinflammatory activity of the protease, we pretreated HUVECs with the PC zymogen and then activated PAR-1 with thrombin. It was found that thrombin downregulates the HMGB1-mediated induction of both TNF-${\alpha}$ and IL-6 and inhibits the activation of both p38 MAPK and NF-${\kappa}B$ in HUVECs pretreated with PC. Furthermore, thrombin inhibited HMGB1-mediated hyperpermeability and leukocyte adhesion/migration by inhibiting the expression of cell adhesion molecules in HUVECs if EPCR was occupied. Collectively, these results suggest the concept that thrombin can initiate proinflammatory responses in vascular endothelial cells through the activation of PAR-1 may not hold true for normal vessels expressing EPCR under in vivo conditions.

Cytotoxic Effects of Sesquiterpene Lactones from the Flowers of Hemisteptia Iyrata B.

  • Ha, Tae-Joung;Jang, Dae-Sik;Lee, Jong-Rok;Lee, Kyung-Dong;Lee, Jun;Hwang, Seon-Woo;Jung, Hwa-Jin;Nam, Sang-Hae;Park, Ki-Hun;Yang, Min-Suk
    • Archives of Pharmacal Research
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    • v.26 no.11
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    • pp.925-928
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    • 2003
  • Four guaia-12,6-olide type sesquiterpene lactones, aguerin B (1), 8$\alpha$-acetoxyzaluzanin C (2), cynaropicrin (3), and deacylcynaropicrin (4), were isolated from the flowers of Hemisteptia Iyrata Bunge. It is the first report on the isolation of compounds 1-4 from Hemisteptia species. All the isolates (1-4) were examined for their cytotoxic activity against SK-OV-3, LOX-IMVI, A549, MCF-7, PC-3, and HCT-15 human cancer cell lines.

대기압에서 발생시킨 헬륨 플라즈마에서의 산소함유량 증가에 따른 폐암세포의 세포내 활성 산소 종 및 세포주기 변화

  • Jo, Hye-Min;Kim, Seon-Ja;Jeong, Tae-Hun;Im, Seon-Hui
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.261.2-261.2
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    • 2014
  • 저온에서 작동하는 대기압 플라즈마 젯은 생체 조직에의 플라즈마 처리를 가능하게 한다. 이에 이온과 전자, 활성 종, 전기장, UV 등을 발생시키는 플라즈마를 암세포에 처리하여 그에 따른 변화를 관찰하였다. 모세관 타입의 젯에 산소를 반응기체로 흘려주어 헬륨 내 산소 함유량에 따른 활성 산소종의 생성을 확인하였다. 대기압 플라즈마에 의해 생성되는 활성 산소 종(OH, O, electronically excited O (1D), O2 ($1{\Delta}g$) 등)이 세포에 산화 스트레스를 유발할 것이라 예상되어 인체의 폐암 세포[Human lung cancer cell, A549]에 펄스파의 헬륨-산소 플라즈마를 처리한 후, 세포 내 활성 산소 종의 증가량을 비교하였다. 그 결과 적은 양의 산소를 추가하였을 때 세포 내 활성 산소 종의 농도가 증가되었다. 이때 플라즈마에서 발생되는 활성 산소 종(Reactive Oxygen Species, ROS)들은 광 방출 스펙트럼(Optical Emission Spectroscopy)로 확인하였고, 세포내 활성 산소 종은 DCF-DA 염색을 통하여 분석하였다. 이러한 헬륨-산소 플라즈마가 세포 성장의 어떠한 시기에 영향을 미치는지를 알아보기 위하여 세포주기 변화를 분석한 결과, 플라즈마 처리 9시간 후부터 G2/M 주기에 머물러 있음을 확인하였다.

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Compounds from the Seeds of Myristica fragrans and Their Cytotoxic Activity

  • Cuong, To Dao;Lim, Chae-Jin;Trang, Tran Thi Thu;Bae, Yoon-Ho;Thu, Nguyen Van;Tung, Nguyen The;Hung, Tran Manh;Woo, Mi-Hee;Choi, Jae-Sue;Min, Byung-Sun
    • Natural Product Sciences
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    • v.18 no.2
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    • pp.97-101
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    • 2012
  • Six lignan compounds, 1-(17,21-dihydroxyphenyl)-9-(12,13-dihydroxyphenyl)-1-nonanone (malabaricone C) (1), 7'-(3',4'-methylenedioxyphenyl)-8,8'-dimethyl-7-(3,4-dihydroxyphenyl)-butane (2), 7'-(3',4'-dimethoxyphenyl)-8,8'-dimethyl-7-(3-methoxy-4-hydroxyphenyl)-butane (3), 7-(4-hydroxy-3-methoxyphenyl)-7'-(3',4'-methylenedioxyphenyl)-8,8'-lignan-7-methyl ether (4), (+)-erythro-(7S,8R)-${\Delta}^{8^'}$-7-hydroxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan (5), and (+)-erythro-(7S,8R)-${\Delta}^{8^'}$-7-acetoxy-3,4,3',5'-tetramethoxy-8-O-4'-neolignan (6), were isolated from the seeds of Myristica fragrans. The chemical structures of these compounds were determined on the basis of spectroscopic analyses including 2D NMR. Compounds 1 - 6 were evaluated for their cytotoxic activity against the HL-60, MCF-7, and A549 cancer cell lines in in vitro.

Isolation of Eudesmanolides Derivatives from the Flower of Chrysanthemum coronarium L. (쑥갓 꽃에서 Eudesmanolide 유도체 분리)

  • Lee, Kyung-Dong;Ha, Tae-Joung;Park, Ki-Hun;Yang, Min-Suk
    • Korean Journal of Medicinal Crop Science
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    • v.9 no.4
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    • pp.269-274
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    • 2001
  • Two sesquiterpene lactones were isolated from the flowers of Chrysanthemum coronarium L. by silica gel chromatography and recrystalization. Their structures were determined using various spectroscopic data, and were identified as eudesmanolide derivatives douglanine and reynosin, respectively. This is reported for the first time in this plant. The cytotoxic activity of two compounds showed strong activities against human cancer cell lines such as A549, PC-3 and HCT 116.

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Adaptive Quantization Scheme for Multi-Level Cell NAND Flash Memory (멀티 레벨 셀 낸드 플래시 메모리용 적응적 양자화기 설계)

  • Lee, Dong-Hwan;Sung, Wonyong
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.38C no.6
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    • pp.540-549
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    • 2013
  • An adaptive non-uniform quantization scheme is proposed for soft-decision error correction in NAND flash memory. Even though the conventional maximizing mutual information (MMI) quantizer shows the optimal post-FEC (forward error correction) bit error rate (BER) performance, this quantization scheme demands heavy computational overheads due to the exhaustive search to find the optimal parameter values. The proposed quantization scheme has a simple structure that is constructed by only six parameters, and the optimal values of them are found by maximizing the mutual information between the input and the output symbols. It is demonstrated that the proposed quantization scheme improves the BER performance of soft-decision decoding with only small computational overheads.

Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with cytotoxic activity against human lung adenocarcinoma cells

  • Yu, Jae Sik;Roh, Hyun-Soo;Baek, Kwan-Hyuck;Lee, Seul;Kim, Sil;So, Hae Min;Moon, Eunjung;Pang, Changhyun;Jang, Tae Su;Kim, Ki Hyun
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.562-570
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    • 2018
  • Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

Studies on Immunomodulatory and Antioxidant Activities of Astragali membranacei Radix according to the Cultivated Years (황기(黃芪)의 재배 년수에 따른 면역 및 항산화 활성 연구)

  • Jung, Chul
    • Korean Journal of Korean Medical Institute of Dermatology and Aesthetics
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    • v.1 no.1
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    • pp.53-90
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    • 2005
  • Purpose: Contents of astragaloside I, II and IV, cytotoxicity, anticancer activity, immunomodulatory activity and antioxidant capacity were to be compared as a function of the cultivated years as one, three, five and seven years. Method: Major components of Astragali membranacei Radix were separated as astragaloside I, astragaloside II, astragaloside IV by HPLC analysis. Cytotoxicity and anticancer activities were measured by MTT and SRB assay. For immunomodulatory activity, the secretion of IL -6 and $TNF-{\alpha}$, NK cell activation and macrophage activation were observed as well as kinetics of responding to human T cells by a microphysiometer. In vitro antioxidant activities were measured by several radical scavenging activities of superoxide anion radican, DPPH, LDL and linoleic acid. For in vivo activity, the activation of SOD, GSH-px, catalase, ALDH and ADH was measured as well the relative weight of liver. Result : 1. For HPLC analysis, the contents of all of astragaloside I, astragaloside II, astragaloside IV were in order of three, five, one and seven years. 2. The cytotoxicity of normal human lung cell line, HEL299 showed lower than 18% in adding 0.25 mg/ml, and 28.9% in adding 1.0 mg/ml of water extract of seven year root. For methanol extracts, three year root showed highest cytotoxicity as 35.2 % and there was no difference between the cultivated years. 3. For anticancer activities, methanol extracts of one and three year roots showed relatively high inhibition of human stomach cancer cells, AGS, breast cancer cells, MCF-7, lung cancer cells, A549 and liver cancer cell, Hep3B as well as high selectivities. 4. The water extract of seven year root could yield high secretion of IL-6 from both human Band T cells while the methanol extracts of three and five year roots secreted high amounts of IL-6 and $TNF-{\alpha}$ from both Band T cells. 5. As a result of in vitro antioxidant activities, both water and methanol extracts from five and seven year roots showed high activities for superoxide anion radical scavenging activity, inhibiting linoleic acid peroxide and contents of total phenols. 6. For in vivo tests, Mn-SOD and GSH-px activities and weight of liver were better in adding seven year root. For ALDH activity one year root was better and for ADH activity five year root. Overall speaking, seven year root showed relatively better antioxidant activities. Conclusion:There was difference of the contents of astragaloside I, astragaloside II, astragaloside IV according to cultivation year. Methanol extract showed better activities of anticancer and immune activation rather than water extract Interestingly enough, for methanol extracts, overall activities were improved as the cultivation year increased. There might be further investigation required for the clinical uses of the results as several biological activities varied according to the cultivated year of Astragali membranacei Radix.

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Non-Polar Myxococcus fulvus KYC4048 Metabolites Exert Anti-Proliferative Effects via Inhibition of Wnt/β-Catenin Signaling in MCF-7 Breast Cancer Cells

  • Park, Juha;Yoo, Hee-Jin;Yu, Ah-Ran;Kim, Hye Ok;Park, Sang Cheol;Jang, Young Pyo;Lee, Chayul;Choe, Wonchae;Kim, Sung Soo;Kang, Insug;Yoon, Kyung-Sik
    • Journal of Microbiology and Biotechnology
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    • v.31 no.4
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    • pp.540-549
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    • 2021
  • The Wnt/β-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/β-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, β-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/β-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/β-catenin pathway.

Increased Cellular NAD+ Level through NQO1 Enzymatic Action Has Protective Effects on Bleomycin-Induced Lung Fibrosis in Mice

  • Oh, Gi-Su;Lee, Su-Bin;Karna, Anjani;Kim, Hyung-Jin;Shen, AiHua;Pandit, Arpana;Lee, SeungHoon;Yang, Sei-Hoon;So, Hong-Seob
    • Tuberculosis and Respiratory Diseases
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    • v.79 no.4
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    • pp.257-266
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    • 2016
  • Background: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to $NAD^+$ by various quinones and thereby elevates the intracellular $NAD^+$ levels. In this study, we examined the effect of increase in cellular $NAD^+$ levels on bleomycin-induced lung fibrosis in mice. Methods: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with ${\beta}$-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor ${\beta}1$ (TGF-${\beta}1$) and ${\beta}$-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). Results: ${\beta}$-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-${\beta}1$, ${\alpha}$-smooth muscle actin accumulation. In addition, ${\beta}$-lapachone showed a protective role in TGF-${\beta}1$-induced ECM expression and EMT in A549 cells. Conclusion: Our results suggest that ${\beta}$-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-${\beta}1$-induced EMT in vitro, by elevating the $NAD^+$/NADH ratio through NQO1 activation.