• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2113-2118
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• 2013

Aim and Background: Cervical cancer remains the third most common cancer in women globally after breast and colorectal cancer. Well-characterized biomarkers are necessary for early diagnosis and to predict metastatic progression and effective therapy. MiRNAs can regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or degradation in tumor cells. The present study was conducted to assess expression of miR93, miR200a, RECK, MMP2, MMP9 in invasive cervical carcinoma, and analyze their clinical significance. Method: A total of 116 patients with invasive cervical carcinoma and 100 patients undergoing hysterectomy for benign lesions were retrospectively examined. Quantitative real-time PCR was performed to determine expression of miR93 and miR200a while RECK, MMP2, MMP9 and MVD were assessed by immunohistochemical staining. Results: Cervical carcinoma patients demonstrated up-regulation of miR-93, miR-200a, MMP2 and MMP9, with down-regulation of RECK as compared to benign lesion tissues. RECK was significantly inversely related to invasion and lymphatic metastasis. The 5-year survival rate for patients with strong RECK expression was significantly higher than that with weakly expressing tumors. Conclusion: MiR-93 and miR-200a are associated with metastasis and invasion of cervical carcinoma. Thus together with RECK they are potential prognostic markers for cervical carcinoma. RECK cooperating with MMP2, MMP9 expression is a significant prognostic factor correlated with long-term survival for patients with invasive cervical carcinoma.

• KSBB Journal
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• v.23 no.2
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• pp.142-146
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• 2008

In order to sprout and migrate, cells must secrete proteinases which are degrading the surrounding extracellular matrix. In this study, we examined the effect of mulberry extracts and combination of mulberry extracts and VEGF on human malignant glioma U-373-MG cells. Mulberry extracts induced the secretion of matrix metalloproteinase-9 (MMP-9) and suppressed the secretion of MMP-2 and plasmin. Mulberry extracts inhibited the VEGF-induced MMP-2, MMP-9 and plasmin secretion. It is therefore, suggested that mulberry extracts can suppress the VEGF-induced tumor angiogenesis in U-373-MG cells. Also, mulberry extracts induced the secretion of MMP-9 and plasmin through PI 3'-kinase pathway in U-373-MG cells.

• Journal of Environmental Science International
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• v.15 no.8
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• pp.799-809
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• 2006

Hydrobromic acid salts of new N, N, O tridentate ligands containing phenol, 2-[(2-Methylamino- ethyl- amino)-methyl]-phenol(H-MMP. 2HBr), 5-Bromo-2-[(2-Methylamino-ethylamino)-methyl]-phenol (Br- MMP. 2HBr), 5-Chloro-2-[(2-Methylamino-ethylamino)-methyl]-phenol(Cl-MMP. 2HBr), 5-Methyl-2-[(2-Methylamino-ethylamino)-methyl]-phenol(Me-MMP. 2HBr), 5-Methoxy-2-I(2-Methylamino-ethylamino)- methyl]-phenol(MeO- MMP. 2HBr) and. 1-[(2-Methylamino-ethylamino)- methyl]-naphthalen-2-ol(Nap- MMP. 2HBr) were synthesized. The synthesized ligands were confirmed by C. H. N. atomic analysis, UV-visible and IR spectroscopies, $^1$H NMR, $^{13}$C NMR and mass analysis. The potentiometry study revealed that the proton dissociation constants(logK$_n^H$) of the synthesized ligands and stability constants (logK$_{ML}$, logK$_{LM2}$) of transition metal complexes of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Pb(II) ions occurred in three steps and the order of the calculated overall proton dissociation constants(log$\beta_p$) and stability constants (logK$_{ML}$) of ligands was Br-MMP. 2HBr < Cl-MMP 2HBr < H-MMP. 2HBr < Nap-MMP. 2HBr < Me-MMP. 2HBr < MeO-MMP. 2HBr. The order showed a similar trend to that of Hammett substituent constants($\delta_p$). The synthesized ligands usually form 2:1(ML$_2$) complexes with transition metal ions. The order of the stability constants of each transition metal ions was Co(II) < Ni(II) < Cu(II) ;> Zn(II) ;> Cd(II) ;> Pb(II).

• Journal of Periodontal and Implant Science
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• v.36 no.1
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• pp.85-96
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• 2006

Matrix metalloproteinases (MMPs)는 치주조직내에 존재하는 세포외기질의 유지와 분해에 중요한 역할을 담당하고 있으며 이중 MMP-13은 치주질환의 진행과 깊은 관계가 있다고 알려져 있다. 이번 연구는 치주질환의 진행에 있어서 MMP-13의 활성에 대한 mitogen activated protein(MAP) Kinase의 역할을 구명하기 위해 시행되었다. 백서 치주인대세포에서의 MMP-13 mRNA의 발현은 RT-PCR에 의하여, 그리고 MAP Kinase의 발현은 Western blot에 의하여 측정하였다. $Interleukin-1{\beta}$(IL $-1{\beta}$), Tumor necrosis $factora(TNF-{\alpha})$와 parathyroid hormon(PTH)는 MMP- 13 mRNA 발현을 각각 320%, 180%, 380% 증가시켰으나 bone morphogenetic protein-7(BMP-7)은 MMP-13 mRNA의 발현을 증가시키지 않았다. p38 MAP Kinase 억제제인 SB203580은 IL $-1{\beta}$ 유도 MMP-13의 발현을 약 40% 정도 억제시켰으나, PTH-유도 MMP-13 mRNA의 발현은 억제하지 못했다. IL $-1{\beta}$는 MMP- 13 mRNA의 반감기를 약 2시간 정도로 증가시켰으나, p38 MAP Kinase 억제제로 전처치한 경우에는 반감기가 60분으로 줄어들었다. $IL-1{\beta}$는 p38 MAP kinase와 JNK의 인산화 활성을 증가시켰으나 PTH, $TNF-{\alpha}$와 BMP-7은 p38, JNK, ERK의 활성을 증가시키지 못했다. 이상의 연구결과는 p38 MAP Kinase가 백서 치주인대세포에서의 MMP-13 mRNA 발현을 조절하는데 중요한 역할을 담당함을 시사하였다.

• 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.

• Proceedings of the SCSK Conference
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• 2003.09b
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• pp.12-25
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• 2003

L-camitine ($\beta$ -hydroxy-${\gamma}$ -trimethyl-ammoniumbutyric acid) is a small water-soluble molecule important in mammalian fat metabolism. It is essential for the normal oxidation of fatty acids by the mitochondria, and is involved in the trans-esterification and excretion of acyl-CoA esters. In this paper, to investigate the relationship between aging and L-camitine, we investigated the effects of in vitro MMP inhibition and activity and expression of UVA-induced MMP 1 in human skin fibroblasts. Fluorometric assays of the proteolytic activities of MMP-l were performed using fluorescent collagen substrates. ELISA (enzyme linked immuno sorbent assay), gelatin-substrate zymography, and RT-PCR ELISA techniques were used for the effects of L-camitine on MMP expression and activity, MMP mRNA expression in UVA irradiated fibroblast. L-camitine inhibited the activities of MMP-l in a dose-dependent manner and the $IC_{50}$/ values calculated from semi-log plots were 2.45mM, and L-carnitine showed strong inhibition on MMP-2 (gelatinase) activity in UVA irradiated fibroblast by zymography. Also, UVA induced MMP expression was reduced 40% by treated with L-carnitine, and MMP-l mRNA expression was reduced dose-dependent manner. Therefore L-carnitine was able to significantly inhibition the MMP activity, regulation of MMP expression in protein and mRNA level. All these results suggest that L-carnitine may be useful as new anti-aging cofactor for protection against UVA induced MMP expression and activity.

• Journal of Life Science
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• v.23 no.12
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• pp.1553-1556
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• 2013

Flavonoids are one of the major components found in the peels of citrus fruits. Present evidence has suggested that polymethoxyflavonoids, including nobiletin and tangeretin isolated from Citrus sunki, have many biological properties, such as anti-inflammatory, anti-oxidant, and anti-obesity capabilities. Here, we investigated the effect of Citrus sunki peel extract and its possible mechanisms on oxidative stress-induced MMP-1 expression, a major marker of skin photoaging. $H_2O_2$ induced MMP-1 expression in a dose- and time-dependent manner. Extract of Citrus sunki peel (1-25 ${\mu}g/ml$) dose-dependently decreased MMP-1 mRNA levels. When $H_2O_2$ was combined with Citrus sunki peel extract, the phosphorylation of ERK was further decreased compared to a single treatment with $H_2O_2$ alone. Moreover, U0216, an MEK inhibitor, markedly prevented the production of MMP-1. These data suggest that Citrus sunki peel extract has demonstrated protective activity against oxidative damage on MMP-1 expression, and ERK MAP kinase may be involved.

• Ocean and Polar Research
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• v.41 no.2
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• pp.79-88
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• 2019

In this study, the inhibitory effect of Atriplex gmelinii C. A. Mey. against the activity of MMP-2 and MMP-9 secreted from phorbol-12-myristate-13-acetate (PMA)-stimulated HT-1080 cells was evaluated by gelatin zymography and enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase-chain reaction (RT-PCR), and Western blot assay. Specimens of the halophyte A. gmelinii were extracted twice for 24 hr with methylene chloride ($CH_2Cl_2$), and then twice with methanol (MeOH), in turn. Each extract significantly inhibited the enzymatic activities in gelatin zymography and MMP ELISA kit, and expression of MMP-2 and 9 in mRNA and protein levels. Two crude extracts were combined and then the combined crude extracts were fractionated into n-hexane, 85% aqueous methanol (85% aq.MeOH), n-butanol (n-BuOH), and water ($H_2O$) fractions, according to solvent polarity. Among solvent-partitioned fractions, the 85% aq.MeOH fraction showed the strongest inhibitory effect against MMP-2 and -9 in gelatin zymography and MMP ELISA kit. In RT-PCR, all solvent-partitioned fractions significantly suppressed mRNA expression of MMP-2 and -9. On the other hand, in Western blot assay, all solvent-partitioned fractions except $H_2O$ significantly reduced expression levels of protein. HT 1080 cell migration was most significantly inhibited by the n-BuOH fraction followed by the 85% aq.MeOH and $H_2O$ fractions. These results suggest that A. gmelinii could be used as a potential source to inhibit tumor cell metastasis.

• Genomics & Informatics
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• v.21 no.1
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• pp.9.1-9.13
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• 2023

Matrix metalloproteinase-9 (MMP-9) is a zinc and calcium-dependent proteolytic enzyme involved in extracellular matrix degradation. Overexpression of MMP-9 has been confirmed in several disorders, including cancers, Alzheimer's disease, autoimmune diseases, cardiovascular diseases, and dental caries. Therefore, MMP-9 inhibition is recommended as a therapeutic strategy for combating various diseases. Cinnamic acid derivatives have shown therapeutic effects in different cancers, Alzheimer's disease, cardiovascular diseases, and dental caries. A computational drug discovery approach was performed to evaluate the binding affinity of selected cinnamic acid derivatives to the MMP-9 active site. The stability of docked poses for top-ranked compounds was also examined. Twelve herbal cinnamic acid derivatives were tested for possible MMP-9 inhibition using the AutoDock 4.0 tool. The stability of the docked poses for the most potent MMP-9 inhibitors was assessed by molecular dynamics (MD) in 10 nanosecond simulations. Interactions between the best MMP-9 inhibitors in this study and residues incorporated in the MMP-9 active site were studied before and after MD simulations. Cynarin, chlorogenic acid, and rosmarinic acid revealed a considerable binding affinity to the MMP-9 catalytic domain (ΔG_binding < -10 kcal/ mol). The inhibition constant value for cynarin and chlorogenic acid were calculated at the picomolar scale and assigned as the most potent MMP-9 inhibitor from the cinnamic acid derivatives. The root-mean-square deviations for cynarin and chlorogenic acid were below 2 Å in the 10 ns simulation. Cynarin, chlorogenic acid, and rosmarinic acid might be considered drug candidates for MMP-9 inhibition.

• Journal of Life Science
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• v.26 no.5
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• pp.584-591
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• 2016

Saururus chinensis is a perennial plants, its flavonoid compound is known to exhibit anti-oxidative activity. This study was aimed to investigate the effect of Water Extract and Solvent Fractions of Saururus chinensis on antioxidant, anti-inflammatory and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities. Plant samples were fractionated into hexane, CHCl₃, ethyl acetate, butanol, and water fractions, and each of these was assayed individually. The water fraction showed the highest extraction yield at 9.25%(w/w). Anti-oxidative activity was analyzed by DPPH assay. Cell viability was detected by the MTS assay. Anti-inflammatory activity was assayed by the nitric oxide (NO) production in mouse macrophage Raw 264.7 cells. The activity and mRNA expression of MMP-2 and MMP-9 in human oral squamous carcinoma YD-10B cells were examined by zymography and RT-PCR. As results, MMP-2/-9 activation was increased in PMA induced YD-10B cells. In PMA-treated YD-10B cells, the increased mRNA expression and protein activation of MMP-2/-9 were significantly inhibited in the ethyl acetate fraction. The ethyl acetate fraction showed the highest anti-oxidative activity at 73.38%. The ethyl acetate fraction at non-cytotoxic concentrations significantly exhibited the anti-inflammatory activity of Raw 264.7 cells in dose-dependent manner. In conclusion, these findings demonstrate that the ethyl acetate fraction obtained from a chinensis water extract potentiates a promising therapeutic anti-invasive agent and, therefore, as an anti-cancer drug for cancer prevention and therapy in oral cancer.