• The Korean Journal of Physiology and Pharmacology
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• v.11 no.3
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• pp.85-88
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• 2007

Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. $15{\sim}30min$ prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. $15{\sim}30min$ prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG ire mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.

• 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.

• Journal of Nutrition and Health
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• v.36 no.3
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• pp.280-286
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• 2003

Conjugated linoleic acid (CLA) consists of several geometric isomers of linoleic acid. CLA is found in foods derived from ruminants and exhibits strong anticarcinogenic effects in a variety of animal models. Matrix metalloproteinases (MMPs) play a key role in cancer progression. Specifically, MMP-2 and -9, which hydrolyze the basal membrane type IV collagen, are involved in the initial breakdown of collagen and basement membrane components during tumor growth and invasion. However, the effects of CLA on cancer cell motility and MMP expression and activity are not currently well known. Therefore, the present study examined whether CLA reduces the activity of MMP and cell motility in SW480 and SW620 cells, the human colon cancer cell lines. Gelatin zymography and Western blot analysis revealed that phorbol 12-myristate 13-acetate (PMA) induced the activity and protein expression of Mr 92,000 MMP-9 in both cell lines. To examine whether CLA inhibits the MMP activity, cells were incubated with 100 ngfmL PMA in the presence of various concentrations of CLA. PMA-induced MMP-9 activity was decreased by 20 $\mu$ M CLA in SW480 cells, and by 10 $\mu$ M and 20 $\mu$ M CLA in SW620 cells. Results from the Hoyden chamber assay showed that cell motility was increased by PMA and that PMA-induced cell motility was significantly decreased by 20 $\mu$ M CLA in SW480 cells. These results indicate that CLA may reduce the motility and MMP activity in human colon cancer cells.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.358-363
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• 2004

Matrix metalloproteinases (MMPs) are known to play an important role in photoaging by mediating the degradation of extracellular matrix proteins. In this study, to develop a n ew anti-aging agent, we investigated the antioxidant activity and the inhibitory effect of Melothria heterophylla extract on expression of MMP-1 in UVA-irradiated human dermal fibroblasts and MMP-1 activity. The M.heterophylla extract was found to scavenge radicals and reactive oxygen species (ROS) with the $SC_{50}$ values of $13{\mu}g/ml$ against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and $20{\mu}g/ml$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. UVA-induced MMP-1 expression was reduced about 80% by $100{\mu}g/ml$ of the M.heterophylla extract but MMP-1 Mrna expression was not inhibited. Therefore, we conclude that the M.heterophylla extract significantly inhibits MMP-1 expression at the protein level. Also, the M.heterophylla extract inhibited MMP-1 activity in a dose dependent manner. From these results, we suggest that the M.heterophylla extract can be used as a new anti-aging agent by antioxidant activity, regulation of UVA-induced MMP-1 production, and inhibition of MMP-1 activity.

• Biomedical Science Letters
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• v.14 no.3
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• pp.179-186
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• 2008

Matrix metalloproteinases (MMPs), also designated matrixins, hydrolyze components of the extracellular matrix. These proteinases playa central role in many biological processes, such as embryogenesis, normal tissue remodeling, wound healing, and angiogenesis, and in diseases such as atheroma, arthritis, cancer, and tissue ulceration. In previous data, disruption of the actin cytoskeleton by cytochalasin D (CD) inhibited NO-induced apoptosis, dedifferentiation, cyclooxygenase (COX)-2 expression, and prostaglandin $E_2$ production in chondrocytes cultured on plastic or during cartilage explants culture. In this study, we investigated the effects of the actin cytoskeleton architecture on MMP-2 expression and dedifferentiation by CD in rabbit articular chondrocytes. Rabbit articular chondrocytes were prepared from cartilage slices of 2-weeks-old New Zealand white rabbits by enzymatic digestion. CD was used as a disruptor of actin cytoskeleton. In this experiments measuring CD dose response, primary chondrocytes were treated with various concentrations of CD for 24h. The actin disruption was determined by immunostaining. MMP-2 expression levels were determined by immunoblot analysis and Reverse transcriptase-Polymerase chain reaction (RT-PCR) and MMP-2 activity was determined by gelatin zymography. We found that cell morphological change and up-regulation of MMP-2 expression by CD as determined via immunostaining, gelatin zymography and immunoblotting. Moreover, CD induced MMP-2 transcription was detected by RT-PCR. Also, CD-induced type II collagen expression was inhibited by MMP-2 inhibitor I treatment. Our results indicate that CD up-regulated MMP-2 activation causes dedifferentiation of articular chondrocyte.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6749-6751
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• 2015

Background: Laryngeal cancer is an important malignancy in head and neck area and squamous cell carcinoma (SCC) is the most common type accounting for 95% of cases. Increase in matrix metalloproteinases (MMPs) in different tumors and their correlation with tumor invasiveness has been documented. However, most studies have evaluated MMP-2 and MMP-9 expression and few have evaluated serum levels. The aim of current study was to evaluate serum levels in patients with laryngeal SCC compared to normal subjects and assess any relation with tumor clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included. Serum levels of MMP-2 and MMP-9 were compared between groups and correlations with findings including grade (T) and node involvement (N) were evaluated. Results: Patients with laryngeal SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p=0.03) compared to healthy subjects. Patients with higher T stage (T3,4) had significantly higher MMP-2 (p=0.04) and MMP-9 (p=0.01). There was significant positive correlation between serum levels of MMP-2 with T stage (r=0.45, p=0.04) and lymph node involvement (r=0.563, p=0.01) and between levels of MMP-9 with T stage (r=0.527, p=0.01). Conclusions: Our results showed that compared to healthy subjects, both MMP-2 and MMP-9 are significantly increased in serum of laryngeal SCC cases. MMP-2 was correlated with lymph node involvement while MMP-9 has stronger correlation with T stage compared to MMP-2.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.191-201
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• 2005

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

• Preventive Nutrition and Food Science
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• v.21 no.1
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• pp.38-43
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• 2016

Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that take important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Natural products are on the rise for their potential to provide remarkable health benefits. In this context, halophytes have been of interest in the nutraceutical field with reported instances of isolation of bioactive compounds. In this study, Limonium tetragonum, an edible halophyte, was studied for its ability to inhibit MMP-2 and -9 using HT1080 fibrosarcoma cells. Results showed that L. tetragonum extract was able to inhibit the enzymatic activity and mRNA expression of MMP-2 and -9 according to gelatin zymography and RT-PCR assays, respectively, but it was not able to significantly change the MMP pathway related factors such as tissue inhibitors of metalloproteinases. Also, Mitogen-activated protein kinases pathway-related protein levels and their phosphorylation were assayed. While the phosphorylated p38 levels were decreased, extracellular signal-regulated kinase and c-Jun N-terminal kinase were not affected by L. tetragonum treatment. In conclusion, it was suggested that L. tetragonum contains substances acting as MMP inhibitors on enzymatic activity rather than intracellular pathway intervention, which could be useful for further utilization of L. tetragonum as a source for anti-MMP agents.

• Molecules and Cells
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• v.40 no.10
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• pp.761-772
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• 2017

Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed. In the present study, we found that the tumorigenicity of U87MG in nude mice was totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell proliferation or cell cycle, but impaired the invasion and migration of U87MG cells, most likely through inactivating the extracellular signal-related kinases (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of nuclear factor kappa B ($NF-{\kappa}B$), reducing the level of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its receptor (uPAR) system (ERK1/2-$NF-{\kappa}B$-MMPs/uPA-uPAR), and altering the protein levels of epithelial to mesenchymal transitions (EMT)-associated proteins E-cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma.

• Journal of Life Science
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• v.14 no.2
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• pp.263-268
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• 2004

The sprouting of vascular endothelial cells is an initial step in angiogenesis. Matrix metalloproteinases can associate with integrin on the surface of endothelial cells, thereby promoting angiogenesis. The purpose of this study was to test if fibroblast growth factor-2 (FGF-2) can regulate the sprouting in porcine pulmonary artery endothelial cells. FGF-2 induced sprouting and secretion of MMP-2 and plasmin. FGF-2 also induced the expression of integrin Mac-1, which is inhibited IS20I. Addition of BB-94, a 2-antiplasmin and IS20I inhibited FGF-2-induced sprouting activity. Therefore, FGF-2-induced sprouting activity in PPAECs may be accomplished by secretion of proteinases such as MMP-2 and plasmin and integrin expression.