• Journal of Chest Surgery
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• v.38 no.1 s.246
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• pp.38-43
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• 2005

Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). Material and Method: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. Result: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p<0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p<0.01). Conclusion: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5709-5714
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• 2012

Objective: To evaluate the effects of curcumin on matrixmetalloproteinase-9 (MMP-9) and invasion ability induced by transforming growth factor-${\beta}1$ (TGF-${\beta}1$) in MDA-MB-231 cells and potential mechanisms. Methods: Human breast cancer MDA-MB-231 cells were used with the CCK-8 assay to measure the cytotoxicity of curcumin. After treatment with 10 ng/ml TGF-${\beta}1$, with or without curcumin (${\leq}10{\mu}M$), cell invasion was checked by transwell chamber. The effects of curcumin on TGF-${\beta}1$-stimulated MMP-9 and phosphorylation of Smad2, extracellular-regulated kinase (ERK), and p38 mitogen activated protein kinases (p38MAPK) were examined by Western blotting. Supernatant liquid were collected to analyze the activity of MMP-9 via zymography. Following treatment with PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38MAPK, Western blotting and zymography were employed to examine MMP-9 expression and activity, respectively. Results: Low dose curcumin (${\leq}10{\mu}M$) did not show any obvious toxicity to the cells, while $0{\sim}10{\mu}mol/L$ caused a concentration-dependent reduction in cell invasion provoked by TGF-${\beta}1$. Curcumin also markedly inhibited TGF-${\beta}1$-regulated MMP-9 and activation of Smad2, ERK1/2 and p38 in a dose- and time-dependent manner. Additionally, PD98059, but not SB203580, showed a similar pattern of inhibition of MMP-9 expression. Conclusion: Curcumin inhibited TGF-${\beta}1$-stimulated MMP-9 and the invasive phenotype in MDA-MB-231 cells, possibly associated with TGF-${\beta}$/Smad and TGF-${\beta}$/ERK signaling.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.3
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• pp.137-145
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• 2009

As an efficient controlled release system for rhBMP-2, a functional nanoparticle-hydrogel complex, incorporated with matrix metalloproteinase(MMP) sensitive peptide cross-linker, was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase(ALP) activity and mineral contents analysis, based on the rat calvarial critical size defect(8mm in diameter) model. Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded MMP sensitive hyaluronic acid(HA) based hydrogel-Nanoparticles(NP) complex, as compared to only MMP HA, the MMP HA-NP without rhBMP-2, or even with the rhBMP-2. These improvements included the formation pattern of bone and functional marrow, the degree of calcium quantification, and the ALP activity. These results indicate that the MMP sensitive HA with nano-particle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced rhBMP-2 scaffold.

• Microbiology and Biotechnology Letters
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• v.42 no.2
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• pp.194-201
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• 2014

Clitocybin A is a novel anti-wrinkle cosmetic agent produced by the strain from a Korean native mushroom Clitocybe aurantiaca. In this study, fermentation, extraction, and purification conditions for a large scale production of clitocybin A were optimized, and its cytotoxicity and inhibition activity on the expression of matrix metalloproteinase-1 (MMP-1) were characterized. The mass production of anti-wrinkle agent was achieved according to the 300 L fermentation process with a fed-batch cultivation using the modified yeast-maltose (YM) broth, and a total of 12.5 kg of cell mass was obtained in a 120 L culture broth for 14 days. After extraction and purification, clitocybin A was identified by HPLC. The cytotoxicity of clitocybin A was examined by the MTT assay. When assayed at 100 and 200 ${\mu}g/ml$ concentrations, clitocybin A showed no cytotoxicity, demonstrating safety. The inhibition activity of clitocybin A on the expression of MMP-1 was examined against UV irradiation. Oleanolic acid (control group) showed a relatively low MMP-1 inhibiting activity (ca. 16.7%) at 10 ${\mu}g/ml$ and showed increased cytotoxicity at higher concentrations. In contrast, clitocybin A showed no cytotoxicity at 100 ${\mu}g/ml$, and exhibited a relatively high MMP-1-inhibiting activity (33.1%). These findings indicate that clitocybin A may be a safe and effective anti-wrinkle agent for use in functional cosmetics.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.385-390
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• 2010

Excessive extracellular matrix (ECM) accumulation is the main feature of chronic renal disease including diabetic nephropathy. Plasminogen activator inhibitor (PAI)-1 is known to play an important role in renal ECM accumulation in part through suppression of plasmin generation and matrix metalloproteinase (MMP) activation. The present study examined the effect of PAI-1 antisense oligodeoxynucleotide (ODN) on fibronectin upregulation and plasmin/MMP suppression in primary mesangial cells cultured under high glucose (HG) or transforming growth factor (TGF)-${\beta}1$, major mediators of diabetic renal ECM accumulation. Growth arrested and synchronized rat primary mesangial cells were transfected with $1\;{\mu}M$ phosphorothioate-modified antisense or control mis-match ODN for 24 hours with cationic liposome and then stimulated with 30 mM D-glucose or 2 ng/ml TGF-${\beta}1$. PAl-1 or fibronectin protein was measured by Western blot analysis. Plasmin activity was determined using a synthetic fluorometric plasmin substrate and MMP-2 activity analyzed using zymography. HG and TGF-${\beta}1$ significantly increased PAI-1 and fibronectin protein expression as well as decreased plasmin and MMP-2 activity. Transient transfection of mesangial cells with PAI-1 antisense ODN, but not mis-match ODN, effectively reversed basal as well as HG- and TGF-${\beta}1$-induced suppression of plasmin and MMP-2 activity. Both basal and upregulated fibronectin secretion were also inhibited by PAI-1 antisense ODN. These data confirm that PAI-1 plays an important role in ECM accumulation in diabetic mesangium through suppression of protease activity and suggest that PAI-1 antisense ODN would be an effective therapeutic strategy for prevention of renal fibrosis including diabetic nephropathy.

• Journal of Periodontal and Implant Science
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• v.30 no.1
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• pp.51-65
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• 2000

Extracellular matrix component is degraded by enzymes of thematrix metalloproteinases(MMPs). MMPs are produced by both hemopoietic and structural cells. Increased activity of MMP-3 in periodontium is strongly associated with inflammatory periodontal disease. The purpose of the present study was to estimate the effect of BMP-7 on regeneration of periodontium. The optical density was measured by microwell plate reader at 450 nm.The difference of the optical density and the relative activity ofMMP-3 according to the concentration were statistically analyzed by one way ANOVA. The results were as follows: 1. Tetracycline-HCl showed the tendency to inhibit the activity of MMP-3 at the concentration lower than $25{\mu}g/ml$. 2. Doxycycline-HCl inhibited significantly the activity of MMP-3 at the concentration lower than $100{\mu}g/ml$. 3 . Minocycline-HCl inhibited the activity of MMP-3 at the concentration in the range of 10 to 200${\mu}g/ml$. Within the limit of the present study, the above results suggested that bone morphogenetic protein-7 may play a important role in development of periodontium.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.37 no.1
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• pp.17-28
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• 2024

Objectives : This study was conducted to reveal the scientific mechanism of the anti-skin aging activity of Kyung-Ok-Ko(KOK), which is highly useful as a Korean traditional medicine and functional food. Methods : The skin wrinkle and aging inhibitory activity of KOK was confirmed through in vitro experiments of human dermal fibroblast neonatal cell(HDFn) and in vivo of C. elegans, and hairless mouse(SKH-1). Results : The amount of the C-terminus of the collagen precursor in the HDFn cell culture medium treated with KOK using an enzymes-linked immunoassay kit. The group treated with KOK 200㎍/㎖ was a 28.3% increase of collagen precursor compared to the control group. KOK showed inhibitory activity of MMP-1 compared to the control group at a concentration of 200㎍/㎖. In addition, KOK 200㎍/㎖ showed significant inhibitory activity of thermal stress and an oxidative stress compared to the control group in C. elegans. Furthermore, KOK showed a concentration-dependent(100mg/kg and 500mg/kg) anti-wrinkle formation effect in UV-irradiated hairless mouse(SKH-1). Additionally, when KOK was administered to UV-irradiated hairless mice, an increase in procollagen -1 and -3 genes expression was observed, and mmp-1 and mmp-9 genes, which increase collagen decomposition, decreased with the administration of KOK. Conclusions : The skin aging inhibition mechanism of Kyung-Ok-Ko(KOK) is presumed to be achieved through suppressing thermal stress and oxidative stress, suppressing mmp-1 and mmp-9 genes, and increasing procollagen-1 and procollagen-3.

• Journal of Life Science
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• v.16 no.6
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• pp.964-971
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• 2006

The cancer cells, characterized by local invasion and distant metastasis, are very dependant on extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Among the human MMPs, matirx metalloproteinase-2 (MMP-2) and matrix metalloproteinse-9 (MMP-9) are key enzymes that degrade type IV collagen of the matrix. Here, we studied the effect of disulfiram, an anti-tumor compound, on the suppression of the tumor invasion and the activity of MMP-2, MMP-9 in human osteosarcoma cells (U2OS). Disulfiram had the type IV collagenase inhibitory activity, the effect of inhibition of gene and protein expression, and these inhibitions were responsible for blocking invasion through cell mediated and non-cell mediated pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9, and regulated the invasion of U2OS, Caki-1 and Caski. These observations raise the possibility of clinical therapeutic applications for disulfiram used as a potential inhibitor of cancer invasion.

• The Korean Journal of Food And Nutrition
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• v.25 no.4
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• pp.713-718
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• 2012

The purpose of this study was to examine the anti-metastatic effect of Juniperus chinensis extract by inhibition of galectin-3 expression. For this study, we carried out the experiment of galectin-3 expression assay and in vivo metastasis mouse model bearing colon 26-M3.1 lung carcinoma, and also MMP-1, MMP-2 and MMP-9 inhibitory assays relating metastasis mechanism. J. chinensis extract significantly showed the inhibitory effect of basal expression and MNNG-induced expression of galectin-3 in colon 26-M3.1 lung carcinoma at the all tested doses (5, 50 and $500{\mu}g/m{\ell}$). In case of the inhibition of MMP-1, MMP-2 and MMP-9, the weak activity was showed at the doses of 50 and $500{\mu}g/m{\ell}$ and was not detected at the dose of $5{\mu}g/m{\ell}$. However, J. chinensis extract significantly showed the anti-metastatic activity on mouse mode bearing colon 26-M3.1 lung carcinoma. Therefore, this study strongly suggests that J. chinensis is a potent inhibitor of galectin-3 expression, and holds great promise for use in inhibiting metastasis induced by elevated expression of galectin-3.

• Applied Biological Chemistry
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• v.47 no.2
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• pp.222-227
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• 2004

Effects of the extracts from bran part of the pigmented rices on inflammation was evaluated by determining their inhibitory action on the production of nitric oxides, histamines and matrix metalloproteinase(MMP) from inflammatory leukocytes. Effects on the production of nitric oxides in a macrophage cell line, RAW264.7 cells, were determined, demonstrating that any significant difference was not detected between the normal rice and the pigmented rice extracts. Inhibitory effects on the histamine-release from a basophilic cell line, RBL-2H3, were examined, showing 3.6 to 5.4-fold increase in the inhibitory activity compared to that of the normal rices. Among the pigmented rice cultivars tested, especially, inhibitory activity of LK1-3-6-12-1-1 was the greatest. Using RAW264.7 cells, we examined the effect of the pigmented rice extracts on the MMP activity. The results showed that the enzyme activity increased with the increasing concentration of the normal rice extract. However, the pigmented rice extracts, except LK1A-2-12-1-l, acted to decrease the MMP activity with their increasing concentrations. The results described above showed the superiority of the pigmented rice extracts in inhibition on release of histamine and MMP, pivotal factors for causing inflammatory responses, from the leukocytes.