• Food Science of Animal Resources
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• v.35 no.3
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• pp.413-420
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• 2015

The aim of our study was to evaluate the potential benefits of an oral supplement containing porcine placenta extract (PPE) on skin parameters related to cutaneous physiology and aging. PPEs were administered orally to hairless mice for 12 wk. The effects of oral PPE administration on skin water-holding capacity and Transepidermal Water Loss (TEWL) were similar to those of oral collagen (HYCPU2) administered as a positive control. Magnified photographs and replica images showed a reduction in UVB-induced wrinkle formation after collagen and PPE treatments. PPE treatments ameliorated the thicker skin surface that results from UVB exposure, based on a histological examination of skin tissue. The groups that were orally administered PPE (0.05%, OL; 0.1%, OH group) showed significantly reduced Matrix Metaloproteinase-2 (MMP-2) mRNA expression levels compared with the UVB control (Con), by 33.5% and 35.2%, respectively. The mRNA expression of another collagen-degrading protein, MMP-9, was also significantly lower in the groups that received oral administration of PPE (especially in the OH group) than in the control group. Additionally, oral administration of PPE significantly upregulated tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 mRNA expression levels compared with expression levels in the control group (p<0.05). This indicates that orally administered PPE activated the expression of Timp-1 and -2, inhibitors of MMP, which is responsible for collagen degradation in skin. Taken together, we propose that long-term oral administration of PPE might have a beneficial effect with respect to skin photo-aging.

• Preventive Nutrition and Food Science
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• v.20 no.3
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• pp.153-161
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• 2015

Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that have important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Marine plants are on the rise for their potential to provide natural products that exhibit remarkable health benefits. In this context, brown algae species have been of much interest in the pharmaceutical field with reported instances of isolation of bioactive compounds against tumor growth and MMP activity. In this study, eight different brown algae species were harvested, and their extracts were compared in regard to their anti-MMP effects. According to gelatin zymography results, Ecklonia cava, Ecklonia bicyclis, and Ishige okamurae showed higher inhibitory effects than the other samples on MMP-2 and -9 activity at the concentrations of 10, 50, and $100{\mu}g/mL$. However, only I. okamurae was able to regulate the MMP activity through the expression of MMP and tissue inhibitor of MMP observed by mRNA levels. Overall, brown algae species showed to be good sources for anti-MMP agents, while I. okamurae needs to be further studied for its potential to yield pharmaceutical molecules that can regulate MMP-activity through cellular pathways as well as enzymatic inhibition.

• BMB Reports
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• v.36 no.1
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• pp.128-137
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• 2003

Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, rheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involves a cascade of linked, sequential steps that involve multiple host-tumor interactions. Specifically, MMPs are involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot perform successful metastasis. The activities of MMPs are tightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review.

• Journal of Nutrition and Health
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• v.54 no.4
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• pp.412-421
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• 2021

Purpose: Thioacetamide (TAA) produces reactive oxygen species (ROS) in the liver, and the generated ROS induces liver injury through inflammatory reactions. The current study was undertaken to investigate the hepatoprotective effect of Artemisiae Capillaris Herba water extract (AC), imparted via its antioxidant activity, in an animal model of TAA-induced liver injury. Methods: Animal experiments were conducted in 5 groups: normal, control (TAA 200 mg/kg), SM (TAA 200 mg/kg + silymarin 100 mg/kg), ACL (TAA 200 mg/kg + AC 100 mg/kg), ACH (TAA 200 mg/kg + AC 200mg/kg). TAA (intraperitoneal) and treatment compounds (per oral) were administered for 3 days. Serum levels of ammonia concentration and myeloperoxidase (MPO) activity were subsequently measured. Liver tissues were subjected to western blot analysis for measuring the oxidative stress (NADPH oxidase), anti-oxidative activity (Nrf2, heme oxygenase-1 [HO-1], superoxide dismutase [SOD], catalase, and GPx-1/2), tissue inhibitors of metalloproteinase (TIMP)-1, and matrix metalloproteinases (MMPs) protein expressions. Results: Serum ammonia levels and MPO activity were significantly increased in the TAA-induced control group, whereas groups administered AC treatment showed markedly reduced levels. Western blot analysis revealed significantly increased NOX2 and p22^phox expressions, (oxidative stress-related factors) in the TAA-induced control group. These levels were determined to be significantly decreased after AC exposure. Moreover, antioxidant-related factors including Nrf2, HO-1, SOD, catalase, and GPx-1/2 were significantly decreased in the control group and increased in the AC treated groups. In addition, MMP expressions were significantly suppressed in the AC treatment group due to increased levels of TIMP-1. Conclusion: Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22^phox) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced liver injury.

• The Journal of Internal Korean Medicine
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• v.37 no.1
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• pp.65-76
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• 2016

Objectives: The purpose of this study was to identify the inhibitory effects of Hwangheuk-san (HHS), a Korean multi-herb formula comprising four medicinal herbs, on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, using the human bladder cancer 5637 cell line.Methods: Cell viability, motility, and invasion were assessed by 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphnyl-2H-tetrazolium bromide (MTT), wound healing migration, and Transwell assays, respectively. Gene expression was detected by Western blot analysis. In addition, the activities of matrix metalloproteinases (MMPs) and the values for transepithelial electrical resistance (TER) were analyzed using a Gelatinase Activity Assay Kit and an Epithelial Tissue Voltohmmeter, respectively.Results: Our data indicated that within the concentration range that was not cytotoxic, HHS effectively inhibited the cell motility and invasiveness of 5637 cells. HHS markedly decreased the expression and activity of MMP-2 and MMP-9, which was associated with unregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. Further investigation revealed that phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT was decreased in HHS-treated 5637 cells, and a PI3K/AKT inhibitor synergistically reduced the inhibition of migration and invasion and also inactivated MMP-2 and MMP-9. Moreover, HHS increased the tightening of tight junctions (TJs), which was demonstrated by an increase in the TER, and reduced the expression the levels of claudin family members (claudin-3 and -4), which are major components involved in the tightening of TJs.Conclusions: The present findings demonstrated that HHS attenuated the migration and invasion of bladder cancer 5637 cells by modulating the activity of the PI3K/Akt signaling pathway and also through TJ tightening.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2087-2093
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• 2012

Previous evidence showed ${\beta}1$, 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of ${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in ${\beta}3GnT8$. Here we showed that cell proliferation was increased in ${\beta}3GnT8$ overexpressed cells but decreased in ${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in ${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of ${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$), whereas ${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of ${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the ${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.8
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• pp.1167-1174
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• 2013

Cancer cells exhibit increased demand for glutamine-derived carbons to support anabolic processes. Indeed, the spectrum of glutamine-dependent tumors and the mechanisms through which glutamine supports cancer metabolism remain areas of active investigation. In the present study, we investigated the effects of glutamine deprivation on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human prostate carcinoma LnCap cells. Glutamine deprivation markedly inhibited cell motility and invasiveness in a time-dependent manner. The anti-invasive activity of glutamine deprivation was associated with an increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance (TER). The activities of matrix metalloproteinase (MMP)-2 and MMP-9 were inhibited in a time-dependent fashion by glutamine deprivation, which was correlated with a decrease in expression of their mRNA and proteins and up-regulation of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, glutamine deprivation repressed the levels of the claudin family members, which are major components of TJs that play a key role in the control and selectivity of paracellular transport. Moreover, the levels of E-cadherin, a type I transmembrane glycoprotein, and snail, an epithelial to mesenchymal transition regulator and zinc finger transcription factor, were markedly modulated by glutamine deprivation. Taken together, these findings suggest that TJs and MMPs are critical targets of glutamine deprivation-induced anti-invasion in human prostate carcinoma LnCap cells.

• Applied Biological Chemistry
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• v.46 no.1
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• pp.60-65
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• 2003

MMP-1 inhibitory compounds were isolated from 120 Korean traditional edible plants. UP- 1 activity significantly increased linearly with increasing UVB dose in normal human foreskin fibroblast HS68 cell, showing maximum activity at approximately 35 $mJ/cm^2$, whereas in HaCaT cell, normal human keratinocyte, no increase was observed. Maximum secretion of MMP-1 after UVB treatment occurred around 36-48 k after treatment. MMP-1 inhibitory compound isolated from cold-water fraction of Cataegus pinnatifida Bunge showed the mort potent activity. The MMP-1 inhibitory compound was deduced as a peptide based on the fact that pronase digestion decreased the activity whereas periodate oxidation did not. The most potent UP- 1-inhibitory protein, CP-2Va-2, showing an activity of 88.5% against MMP-1, was isolated through sequential column chromatography on DEAE-Toyopearl 650C, Butyl-Toyopearl 650M, and Bio-Gel P-30. Molecular weight of CP-2Va-2 determined through high performance liquid chromatography and SDS PACE was 19 and 20 kDa. respectively, signifying a monomeric structure.

• Journal of Periodontal and Implant Science
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• v.34 no.1
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• pp.139-148
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• 2004

MMPs(Matrix metalloproteinases)는 치주질환에서 주된 조직파괴단백분해효소인 것은 알려져 있고 TIMPs(Tissue inhibitor of Matrix metalloproteinase)는 MMPs의 작용을 억제한다라고 알려져 있다. 이 둘간의 불균형으로 인해서 조직파괴가 더 가속화될 수 있다. 이 두 연구의 목적은 ELISA kit를 사용하여 특정 MMPs(1,2,3,8,9,13)과 TIMPs(1,2)의 양이 건강한 환자와 비교하여서 치주염 환자에서 달라지는지 알아보고 MMPs(1,2,3,8,9,13), TIMPs(1,2)와 치은열구깊이와 GI score와의 관계를 알아보기로 한다. 8명의 만성 치주염 환자와 4명의 급속진행형 치주염 환자가 실험군으로 참여하였고 5명의 건강한 치주조직을 환자가 대조군으로 참여하였다. 임상적인 측정은 GI score와 치주낭측정을 통하여 이루어졌다. 8명의 만성 치주염을 가진 환자와 4명의 급속진행형 치주염을 가진 환자에서 각각 치주낭 깊이가 3mm이하인 부위에서 6개의 치은열구액 표본과 치주낭 깊이가 6mm 이상인 곳에서 6개의 치은열구액 표본을 채취하였다. 건강한 치주조직을 가진 5명의 환자는 단지 치주낭깊이가 3mm 이하인 건강한 부위에서만 치은열구액 표본을 제공하였다. MMPs(1,2,3,8,9,13)과 MIMPs(1,2)의 측정은 Human Biotrack ELISA kit를 사용하여서 측정하였다. 통계처리는 MMPs, MIMPs의 실험군과 대조군의 차이는 Kruskal-Wallis test를 사용하였고 MMPs, TIMPs와 치주낭 깊이와 GI score의 관계정도는 Pearson's correlation coefficient를 사용하였다. 실험결과 대조군과 비교하여 만성 치주염 환자에서 치주낭 깊이가 6mm 이상인 부위에서 MMP9의 수치가 통계적으로 유의할만하게 높았으며(p=0.04) MIMP2의 수치가 대조군과 비교하여 치주낭 깊이가 3mm 이하인 부위를 가진 만성치주염 환자에서 통계적으로 유의할만하게 높았다(=0.049). MMPs(1,2,3,8,9,13), MIMPs(1,2)의 활동성과 치주낭 깊이의 관계에서 둘간의 통계적으로 유의할만한 관계는 존재하지 않았으나 MMP1(r=0.35)과 MMP2(r=0.31)가 상대적으로 높은 관계를 보였다. 또한 MMPs(1,2,3,8,9,13), MIMPs(1,2)의 활동성과 GI score의 관계에서도 둘간의 통계학적으로 유의할만한 관계는 존재하지 않으나 MMP1(r=0.4), MMP2(r=0.29), MMP9(r=0.26)가 상대적으로 높은 관계를 보였다. 이 실험의 결과로 볼 때 MMP9가 만성치주염 환자의 질환이 있는 부위에서만 염증의 지표가 될 수 있으며 MIMP2가 만성치주염 환자의 염증이 없는 부위에서 높은 농도로 존재하는 것으로 보아서 MIMP2가 MMPs에 대한 억제작용을 하여서 염증의 진행을 방해하는 역할을 한다라고 볼 수 있다.