• 한국식품영양과학회지
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• 제41권1호
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• pp.14-19
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• 2012

발아기간에 따른 발아 벼 추출물의 항산화성분, 항산화활성 및 암세포주 성장억제효과를 살펴보았다. 발아는 0, 2, 4, 6 및 8일 동안 진행하였으며, 발아 후 70% 에탄올로 추출물을 제조하였다. 발아가 진행됨에 따라 항산화성분 및 항산화활성은 2~4일까지는 증가하였다가 그 이후에는 감소하였다. 총 폴리페놀 함량은 발아 4일차에서 4.05 mg/g으로 가장 높았으며, DPPH 라디칼 소거능은 0, 2, 4, 6 및 8일차 각각 29.25, 34.82, 31.17, 26.27 및 18.51%로 발아 2일차에 가장 높았으며, 총 항산화력은 발아기간별로 각각 3.05, 3.17, 3.84, 2.43 및 2.167 mg AA eq/100 g으로 발아 4일차에서 가장 높게 나타났다. 환원력 또한 발아 4일차에 1.25로 가장 높게 나타났다. 암세포주 성장억제효과는 위암세포주(AGS) 보다 대장암세포주(HCT-116)에서 높게 나타났다. 이상의 결과로부터 생리활성 증가를 위해서 벼를 발아시킬 경우3~4일이 적당한 것으로 판단되며, 추후 새로운 물질의 생성과 생리활성 성분들에 대한 연구가 더 진행되어야 할 것으로 판단된다.

• 한국식품위생안전성학회지
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• 제21권3호
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• pp.181-188
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• 2006

Tumor necrosis ftctor-alpha$(TNF-{\alpha})$는 세포의 고사, 염증 및 면역 등의 다양한 생물학적 기능에 대한 역할을 한다. PTEN 역시 세포의 성장과 증식 그리고 세포의 유주와 분화 등의 세포학적인 다양한 기능을 갖는다 그러므로 이들 두 분자들 사이의 상호관계가 있을 것으로 제안되고 있으며, $TNF-{\alpha}$는 사람의 대장세포 주인 HT-29에서 nuclear factor-kappa $B(NF-{\kappa}B)$ 경로를 통해 PTEN downregulate 기능이 있는 것으로 알려져 왔다. 그러나 저자 등은 본 연구에서 HL-60 cells에서 $TNF-{\alpha}$가 $NF-{\kappa}B$를 통해 PTEN를 upregulates하는 기존의 반대 현상을 확인하였다. $TNF-{\alpha}$는 HL-60 cells에서 time과 dose의존성 방법으로 PTEN 발현을 증가시켰지만 반응은 p65 anisense oligonucleotide 또는 pyrrolidine dithiocarbamate(PDTC)으로 $NF-{\kappa}B$를 분해함으로 파괴되었다. 따라서 저자 등은 $TNF-{\alpha}$가 $NF-{\kappa}B$경로를 활성화시킴을 확인하였고, $TNF-{\alpha}$를 처리 할 경우 핵에 대하여 p65 전위에 의해 $TNF-{\alpha}$가 활성화됨을 증명하였다. 결국 HL-60세포에서 $NF-{\kappa}B$의 활성화에 따라 PTEN 발현의 upregulation이 유도되는 것으로 결론지었다.

• 한국영양학회:학술대회논문집
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• 한국영양학회 1995년도 추계학술대회 초록
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• Environmental Analysis Health and Toxicology
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• 제22권1호
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• pp.65-71
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• 2007

유산균(Lactic acid bacteria)은 Escherichia coli와 Salmonella typhimurium과 같은 병원균에 대한 항균활성을 나타낼 뿐만 아니라 면역 증강효과를 나타내는 등 인체내에서 건강에 이로운 다양한 역할을 수행하는 것으로 알려졌다. 특히, Pediococcus pentosaseus와 몇몇 Lactobacillus 종으로부터 분리한 항균활성을 나타내는 peptide들인 safelac과 lactopad는 몇몇 암세포주의 성장을 억제하는 것으로 나타났다. 이에, 본 연구에서는 HT-29, SW 480 및 Caco-2와 같은 3종류의 인간의 결장암 세포주에 safelac과 lactopad를 투여하여 이들이 항암효과를 나타낼 수 있는 지를 분석하고자 하였다. XTT assay는 safelaf과 lactopad가 HT-29, SW 480 및 Caco-2의 성장을 억제하는 것으로 나타났으며, 특히, 이들 peptide들을 72시간동안 처리했을 때 나타나는 항암효과는 $3.1{\sim}100mg/mL$의 농도범위에서 유의한 결과를 나타내었으며, 분석한 농도 범위에서 용량 의존적인 방식으로 더 강한 효과를 나타내었다. RAW 264.7 세포주는 cytokine인 tumor-necrosis factor(TNF-${\alpha}$)의 생성에 미치는 이들 peptide들의 효과를 조사하기 위한 대식세포의 모델로써 이용되었다. RAW 264.7 세포주에서 TNF-${\alpha}$의 생성은 이들 peptide들에 의해 48시간 배양시 용량에 의존적인 방식으로 영향을 받는 것으로 나타났다. 따라서, 이러한 발견은 safelac과 lactopad와 같은 유산균으로부터 분리한 항균 peptide들이 결장암 세포에 대한 화학적 예방제로서의 잠재성을 갖고 있음을 시사하는 결과로서 주목된다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.101-101
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• 2003

Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.987-991
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• 2013

Aim: To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26 cells. Methods: In this study, we established an MHC class II molecule-expressing murine colon cancer cell line (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results in vivo were tested and monitored. Results: Exosomes from CT26-CIITA cells were found to contain a high level of MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantly increased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells. In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA-Exo enhanced splenocyte proliferation and IFN-${\gamma}$ production of CD4+T cells, while inhibiting IL-10 secretion. In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-${\alpha}$ and IL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantly inhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumour-bearing mice. Conclusion: Our findings indicate that CT26-CIITA-released exosomes are more efficient to induce anti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes as cancer vaccine candidates.

• Natural Product Sciences
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• 제21권3호
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• pp.162-169
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• 2015

Hamamelis japonica (Hamamelidaceae), widely known as Japanese witch hazel, is a deciduous flowering shrub that produces compact clumps of yellow or orange-red flowers with long and thin petals. As a part of our ongoing search for phenolic constituents from this plant, eleven phenolic constituents including six flavonol glycosides, a chalcone glycoside, two coumaroyl flavonol glycosides and two galloylated compounds were isolated from the flowers. Their structures were elucidated as methyl gallate (1), myricitrin (2), hyperoside (3), isoquercitrin (4), quercitrin (5), spiraeoside (6), kaempferol 4'-O-β-glucopyranoside (7), chalcononaringenin 2'-O-β-glucopyranoside (8), trans-tiliroside (9), cis-tiliroside (10), and pentagalloyl-O-β-D-glucose (11), respectively. These structures of the compounds were identified on the basis of spectroscopic studies including the on-line LCNMR-MS and conventional NMR techniques. Particularly, directly coupled LC-NMR-MS afforded sufficient structural information rapidly to identify three flavonol glycosides (2 - 4) with the same molecular weight in an extract of Hamamelis japonica flowers without laborious fractionation and purification step. Cytotoxic effects of all the isolated phenolic compounds were evaluated on HCT116 human colon cancer cells, and pentagalloyl-O-β-D-glucose (11) was found to be significantly potent in inhibiting cancer cell growth.

• 식품과학과 산업
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• 제52권1호
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• pp.84-99
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• 2019

Dietary fiber is defined as soluble and insoluble polysaccharide consisted in the plant cell wall-associated fibers naturally occurring in fruits, vegetables, and cereal products, and of isolated fibers that are added to processed foods which are also artificially modified. There are so many difference types of dietary fibers as arabinoxylan, polydextrose chicory, oligosccharide. inulin, pectin, bran, cellulose, ${\beta}$-glucan, resistant starch and some seaweed polymers as alginate. Most of them provide many biological benefits in the intestine, as lower risk for developing coronary heart disease, stroke, hypertension, diabetes, obesity and some of the gastrointestinal disease like as colon cancer. And also lowering cholesterol levels, improves glycemic and insulin sensitivity to non-diabetic and diabetic persons including immune system. Beside of many benefits, average consumers in developed and under developing countries take far less amounts of dietary fiber that international organization recommended. Adequate intake of dietary fiber is 14g/1,000kcal base using the energy guide line of 2,000kcal/day for women and 26,000 kcal/day for men, dietary intake is 28g/day of adult women and 36g/day for adult men. The mechanisms behind the reported effects of dietary fiber on metabolic health are not fully well established. It is suggested that changes in intestinal viscosity resulting mucus increasing, macro-nutrients absorption, rate of passage of large intestinal, production of short chain fatty acids by fermentation. Production of gut hormones and changes of microbiota in intestine. It is necessary to do more research in this field in the future and combined interdisciplinary works together.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.265-273
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• 2022

Resistance to chemotherapeutic drugs is a significant problem in the treatment of colorectal cancer, resulting in low response rates and decreased survival. Recent studies have shown that shikonin, a naphthoquinone derivative, promotes apoptosis in colon cancer cells and cisplatin-resistant ovarian cells, raising the possibility that this compound may be effective in drug-resistant colorectal cancer. The aim of this study was to characterize the molecular mechanisms underpinning shikonin-induced apoptosis, with a focus on endoplasmic reticulum (ER) stress, in a 5-fluorouracil-resistant colorectal cancer cell line, SNU-C5/5-FUR. Our results showed that shikonin significantly increased the proportion of sub-G₁ cells and DNA fragmentation and that shikonin-induced apoptosis is mediated by mitochondrial Ca²⁺ accumulation. Shikonin treatment also increased the expression of ER-related proteins, such as glucose regulatory protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (PERK), phospho-eukaryotic initiation factor 2 (eIF2α), phospho-phosphoinositol-requiring protein-1 (IRE1), spliced X-box-binding protein-1 (XBP-1), cleaved caspase-12, and C/EBP-homologous protein (CHOP). In addition, siRNA-mediated knockdown of CHOP attenuated shikonin-induced apoptosis, as did the ER stress inhibitor TUDCA. These data suggest that ER stress is a key factor mediating the cytotoxic effect of shikonin in SNU-C5/5-FUR cells. Our findings provide an evidence for a mechanism in which ER stress leads to apoptosis in shikonin-treated SNU-C5/5-FUR cells. Our study provides evidence to support further investigations on shikonin as a therapeutic option for 5-fluorouracil-resistant colorectal cancer.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권4호
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• pp.337-344
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• 2000

본 연구에서는 MSI와 구강암과의 상관관계를 규명하기 위하여 17례의 구강암에 대하여 12종류의 marker를 이용하여 MSI 빈도를 조사하였으며, 동시에 p53단백의 과발현과 유전자 돌연변이 양상에 대해서도 알아보았다. 그 결과 4종류 이상의 marker에 대해서 MSI가 나타나는 widespread MSI의 경우 임상병리학적으로 뚜렷한 특징이 없었다. 또한 흡연과 MSI 빈도간에도 연관성이 없었으나 흡연은 p53 유전자의 돌연변이를 증가시켜 암화과정을 촉진하는 작용을 하는 것으로 나타났다.