• Title/Summary/Keyword: Tumor promotion

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Study of Anti-inflammatory Effect of CopA3 Peptide Derived from Copris tripartitus (애기뿔소똥구리 유래 CopA3합성 펩타이드의 항염증 효능에 관한 연구)

  • Kim, Hyeon-Jeong;Kim, Dong-Hee;Lee, Jin-Young;Hwang, Jae-Sam;Lee, Joon-Ha;Lee, Seul-Gi;Jeong, Hyeon-Guk;An, Bong-Jeun
    • Journal of Life Science
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    • v.23 no.1
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    • pp.38-43
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    • 2013
  • The objective of this study was to evaluate the effect of the synthetic CopA3 peptide of Copris tripartitus on skin inflammation. Regulatory mechanisms of cytokines and nitric oxide (NO) are involved in the immunological activity of RAW 264.7 cells. Tested cells were treated with different concentrations of CopA3 and further cultured for an appropriate time after lipopolyssacharide (LPS) addition. During the entire experimental period, 5, 25, 50, and 100 ${\mu}g/ml$ of CopA3 had no cytotoxicity. At these concentrations, CopA3 inhibited tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and interleukin-6 (IL-6). CopA3 also inhibited the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). CopA3 inhibited the activity of iNOS and COX-2 by 41% and 59%, respectively, at 100 ${\mu}g/ml$. In addition, CopA3 reduced the release of inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. These results suggest that CopA3 may have significant effects on inflammatory factors and that it may be a potential anti-inflammatory therapeutic agent.

Phytochemical Constituents and Anticancer Activity of Sphagnum palustre Extract (물이끼 추출물의 식물화학적 성분 및 항암활성 연구)

  • Nam, Jung-Hwan;Jeong, Jin-Cheol;Yoon, Young-Ho;Hong, Su-Young;Kim, Su-Jeong;Jin, Yong-Ik;Lee, Ye-Jin;Yoo, Dong-Lim;Lee, Kyung-Tae;Park, Hee-Juhn
    • Korean Journal of Plant Resources
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    • v.24 no.1
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    • pp.40-47
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    • 2011
  • Sphagnum palustre is a semi aquatic moss. S. palustre has been used as Korean traditional medicine to treat cardiac pain and stroke. This study was carried out to analyze phytochemical constituents of S. palustre and investigate the biological activity for the promotion of human health. At first, we isolated seven compounds from the ethanolic extract of this plant, and their structures were characterized by spectroscopic methods. Their structures were characterized to be Coumarin(1), Caffeic acid(2), Quercetin(3), Astragalin(4), Luteolin(5), Chlorogenic acid(6), Rutin(7) were for the first time reported from this source. The ethanol extract from S. palustre which was tested for its anticancer activity against three human tumor cell line by in vitro assay.

Cariporide Enhances the DNA Damage and Apoptosis in Acid-tolerable Malignant Mesothelioma H-2452 Cells

  • Lee, Yoon-Jin;Bae, Jin-Ho;Kim, Soo-A;Kim, Sung-Ho;Woo, Kee-Min;Nam, Hae-Seon;Cho, Moon-Kyun;Lee, Sang-Han
    • Molecules and Cells
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    • v.40 no.8
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    • pp.567-576
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    • 2017
  • The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

Anti-inflammatory Effects of Ethanol Extract from Bark of Acer barbinerve Maxim (청시닥나무 수피 에탄올 추출물의 항염증 효과)

  • Lee, Han-Na;Kim, Jin-Kyu;Kwon, Gyoo-Taik;Shim, Jae-Hoon;Kim, Jong-Dai;YoonPark, Jung-Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.9
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    • pp.1242-1247
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    • 2012
  • Acer barbinerve Maxim belongs to the Aceraceae tree family and is often consumed as an Oriental medicine. In this study, we investigated whether or not ethanol extract from the bark of A. barbinerve Max. (EBA) inhibits lipopolysaccharide (LPS)-induced inflammatory responses in Raw264.7 macrophages. EBA was fractionated using n-hexane, $CH_2Cl_2$, ethyl acetate (EtOAc), and water. Raw264.7 cells were treated with 20 ${\mu}g/mL$ of EBA and the EBA fractions. EBA inhibited LPS-induced nitric oxide (NO) production. Among the three fractions, EtOAc fraction of EBA (EFEBA) was the most effective in inhibiting LPS-induced NO production without significant cytotoxicity in Raw264.7 cells. EFEBA futher reduced LPS-induced expression of inducible NO synthase (iNOS) proteins and its corresponding mRNA. Additionally, EFEBA decreased the mRNA levels of interleukin (IL)-6, IL-$1{\beta}$, and tumor necrosis factor-${\alpha}$ in LPS-treated Raw264.7 cells. Lastly, EFEBA inhibited LPS-induced degradation of the inhibitor of kappaBalpha ($I{\kappa}B{\alpha}$) as well as phosphorylation of p65 nuclear factor-${\kappa}B$ (NF-${\kappa}B$). These results indicate that EFEBA exhibits strong anti-inflammatory effects and can be developed as a potential anti-inflammatory agent.

Anti-oxidant, Anti-inflammatory, and Wound Healing Activities of Selaginella tamariscina Leaf Extract (부처손 잎 추출물의 항산화, 항염 및 피부재생 효능)

  • Kim, Yu-Jin;Lee, Ji-An
    • Journal of Convergence for Information Technology
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    • v.11 no.4
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    • pp.194-202
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    • 2021
  • The leaves of Selaginella tamariscina were used for the treatment of many diseases in traditional medicine. In the study, antioxidant, anti-inflammatory, and wound healing activities of the hot-water extract(STW) and 80%ethanol extract(STE) obtained from S. tamariscina were evaluated. As a result, the polyphenol content of STW and STE were 38.108±0.766 mg/g and 17.927±1.064 mg/g, respectively. The DPPH and ABTS radical scavenging activities with the IC50 values of the STW were over 2 times lower than that of the STE. In the MTT assay, RAW264.7 cell viability of two extracts was decreased by about 6% at 1 mg/mL, whereas for HaCaT cell viability increased by 18% at 50 ㎍/mL. In addition, STW and STE suppressed the production of nitric oxide(NO), Tumor-necrosis(TNF)-��. COX-2 and PGE2 in lipopolysaccharide(LPS) induced RAW264.7 cells. Furthermore, the STE showed wound healing effect through the promotion of skin cell migration in TNF-�� stimulated human keratinocytes. These results indicated that the STW and STE have the potential to be used as a new cosmetic active ingredients in skin care.

Effect of Angelicae Gigantis Radix for Inflammatory Response in HaCaT Cells (당귀(當歸) 추출물이 피부 각질형성세포의 염증반응에 미치는 영향)

  • Huh, Jung;Park, Hoyeon;Kim, Eom Ji;Kim, Eun-Young;Sohn, Youngjoo;Jung, Hyuk-Sang
    • The Korea Journal of Herbology
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    • v.37 no.3
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    • pp.9-19
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    • 2022
  • Objectives : Angelicae Gigantis Radix (AG) is a plant of the Ranunculus family. AG have been reported to have various pharmacological effects on human health which include uterine growth promotion, anti-inflammatory, analgesic, and immune enhancement. However, research on dermatitis disease is insufficient. Therefore, we investigated the effects of AG on tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) stimulated HaCaT cell. Methods : To investigate the effect of AG on HaCaT cell, HaCaT cells were pre-treated with AG for 1 hour and then stimulated with TNF-α/IFN-γ. After 24 hours, media and cells were harvested to analyze the inflammatory mediators. Concentration of human interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α in the media were assessed by ELISA. mRNA expression of human thymus and activation-regulated chemokine (TARC), IL-6, and IL-8 were analyzed by RT-PCR. Additionally, the mechanisms of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway were investigated by Western blot. Results : The treatment of AG inhibited gene expression levels of IL-6, IL-8, and TARC and protein expression levels of IL-1β, MCP-1, and GM-CSF. Also, AG significantly reduced extracellular signal-regulated kinase (ERK) phosphorylation and NF-κB translocation in TNF-α/IFN-γ stimulated HaCaT cell. Conclusions : Taken together, these results demonstrate that AG can alleviate inflammatory diseases such as atopic dermatitis by regulating the expression of inflammatory cytokines. Also, it suggest that AG may a promising candidate drug for the treatment of inflammatory disease such as atopic dermatitis.

Enhanced γ-aminobutyric acid and sialic acid in fermented deer antler velvet and immune promoting effects

  • Yoo, Jiseon;Lee, Juyeon;Zhang, Ming;Mun, Daye;Kang, Minkyoung;Yun, Bohyun;Kim, Yong-An;Kim, Sooah;Oh, Sangnam
    • Journal of Animal Science and Technology
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    • v.64 no.1
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    • pp.166-182
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    • 2022
  • Deer antler velvet is widely used in traditional medicine for its anti-aging, antioxidant, and immunity-enhancing effects. However, few studies have reported on the discovery of probiotic strains for deer antler fermentation to increase functional ingredient absorption. This study evaluated the ability of probiotic lactic acid bacteria to enhance the concentrations of bioactive molecules (e.g., sialic acid and gamma-aminobutyric acid [GABA]) in extracts of deer antler velvet. Seventeen strains of Lactobacillus spp. that were isolated from kimchi and infant feces, including L. sakei, L. rhamnosus, L. brevis, and L. plantarum, and those that improved the life span of Caenorhabditis elegans were selected for evaluation. Of the 17 strains, 2 (L. rhamnosus LFR20-004 and L. sakei LFR20-007) were selected based on data showing that these strains increased both the sialic acid and GABA contents of deer antler extract after fermentation for 2 d and significantly improved the life span of C. elegans. Co-fermentation with both strains further increased the concentrations of sialic acid, GABA, and metabolites such as short-chain fatty acids and amino acids. We evaluated the biological effects of the fermented antler velvet (FAV) on the antibacterial immune response in C. elegans by assessing worm survival after pathogen infection. The survival of the C. elegans conditioned with FAV for 24h was significantly higher compared with that of the control worm group fed only normal feed (non-pathogenic E. coli OP50) exposed to E. coli O157:H7, Salmonella typhi, and Listeria monocytogenes. To evaluate the protective effects of FAV on immune response, cyclophosphamide (Cy), an immune-suppressing agent was treated to in vitro and in vivo. We found that FAV significantly restored viability of mice splenocytes and immune promoting-related cytokines (interleukin [IL]-6, IL-10, inducible nitric oxide synthase [iNOS], interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were activated compared to non-fermented deer antlers. This finding indicated the protective effect of FAV against Cy-induced cell death and immunosuppressed mice. Taken together, our study suggests that immune-promoting antler velvet can be produced through fermentation using L. rhamnosus LFR20-004 and L. sakei LFR20-007.

A Study of Microsatellite Instability in Primary Small Cell Lung Cancers by Microsatellite Analysis (원발성 소세포폐암에서 Microsatellite 분석을 이용한 Microsatellite 불안정화에 대한 연구)

  • Cho, Eun-Song;Chang, Joon;Park, Jae-Min;Shin, Dong-Hwan;Kim, Se-Hoon;Kim, Young-Sam;Chang, Yoon-Soo;Cho, Chul-Ho;Kwak, Seung-Min;Lee, Jun-Gu;Chung, Kyung-Young;Kim, Sung-Kyu;Lee, Won-Young;Kim, Se-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.2
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    • pp.180-190
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    • 2000
  • Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

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Anti-inflammatory Effect of Myricetin from Rhododendron mucronulatum Turcz. Flowers in Lipopolysaccharide-stimulated Raw 264.7 Cells (Lipopolysaccharide로 유도된 Raw264.7 cell에서 Rhododendron mucronulatum Turcz. Flower으로부터 분리한 myricetin에 의한 염증 억제효과)

  • Choi, Moo-Young;Hong, Shin-Hyup;Cho, Jun-Hyo;Park, Hye-Jin;Jo, Jae-Bum;Lee, Jae-Eun;Kim, Dong-Hee;Kim, Byung-Oh;Cho, Young-Je
    • Journal of Life Science
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    • v.26 no.11
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    • pp.1245-1252
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    • 2016
  • As a research of inflammation inhibitory activity using natural resource, the inflammation inhibitory activity by purified active compound from Rhododendron mucronulatum flower was experimented. Rhododendron mucronulatum flower components were purified and separated with Sephadex LH-20 and MCI gel CHP-20 column chromatography, Purified compound was confirmed as myricetin by $^1H-NMR$, $^{13}C-NMR$ and Fast atom bombardment (FAB)-Mass spectrum to have inhibition activity on inflammatory factors secreted by Raw 264.7 cells in response to lipopolysaccharide stimulation. Myricetin inhibited nitric oxide (NO) expression in a concentration dependent manner, approximately 40% inhibition was observed at a concentration of $50{\mu}M$. The inhibition effect of myricetin on inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein expression was 20% and 80%, respectively, at a concentration of $25{\mu}M$. Myricetin also inhibited expression of the inflammatory cytokines, tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-6 and prostaglandin $E_2(PGE_2)$ in a concentration dependent manner; a concentration of $50{\mu}M$, 70%, 80%, 80% and 95% inhibition was observed, respectively. Therefore myricetin isolated from Rhododendron mucronulatum flowers is expected to have an anti-inflammatory effect in Raw 264.7 cell induced by lipopolysaccharides. The results can be expected myricetin from Rhododendron mucronulatum flower to use as functional resource for anti-inflammatory activity.

Comparison of Inhibitory Effect of Rice Bran-extracts of the Colored Rice Cultivars on Carcinogenesis (유색미 겨 추출물의 품종간 발암과정 억제효과의 비교)

  • Kang, Mi-Young;Nam, Seok-Hyun
    • Applied Biological Chemistry
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    • v.41 no.1
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    • pp.78-83
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    • 1998
  • Anticarcinogenicity of 12 kinds of colored rice cultivars was investigated in vitro with Ilpumbyeo as a control. Pigment and hexane fractions were prepared from the rice brans through extraction with 80% ethanol containing 0.5% TFA or n-hexane to use subsequent evaluation of their anticarcinogenic effect by determining inhibitory activity against DNA strand scission and tumor promotion, as well as antimutagenic activity using SOS chromotest system. Antimutagenic activity of the pigment fractions was revealed to decrease in order of LK1B4-12-1-1 > Sanghaehanghyulla > HP833-1-3-1-1 > Chokoto14 > Jagwangdo > Jajin > Kilmheugmi > Tiwan-Tsi-C > Heugjinmi > Linsia-Shoea-Dau > Suweon425 > Suweon415. The activity of the hexane fractions decreased in order of LK1B4-12-1-1 > Sanghaehyanghyulla>Ilpunibyeo > HP833-1-3-1-1 > Chokoto14 > Jagwangdo > Jajin > Linsia-Shoea-Dau >Tiwan-Tsi-C > Heugjinmi > Suweon425, Kilimheugmi > Suweon415. Results showed that inhibitory activity against DNA strand scission in the pigment fractions decreased in order of HP833-1-3-1-1 > Tiwan-Tsi-C > Jajin > Chokoto14 > Suweon425 > Heugjinmi > LK1B4-12-1-1 > Suweon415 > Jagwangdo > Kilimheugmi > Linsia-Shoea-Dau > Sanghaehyanghyulla. On the other hand, the activity of the hexane fractions decreased in order of LK1B4-12-1-1 > Suweon 415 > Kilimheugmi > Chokoto14 > Heugjinmi > Jajin > Suweon425 > Tiwan-Tsi-C > Sanghaehyanghyulla a Linsia-Shoea-Dau > Jagwangdo > HP833-1-3-1-1 > Ilpumbyeo. Experiment using the short-term assay for promotor substance showed that inhibitory activity contained in the pigment fractions against rumor promotor TPA decreased in order of Linsia-Shoea-Dau > Kilimheugmi > HP833-1-3-1-1, Suweon425 > Heugjinmi > Jajin > Chokoto14 > Sanghaehyanghylla > Suweon 415 > LK1B4-12-1-1 > Tiwan-Tsi-C > Jagwangdo.

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