• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.873-876
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• 2013

Our aim was to test the hypothesis that preoperative serum levels of matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) levels correlate with pathological features. Serum levels of MMP-7, and MMP-9 and TIMP-1 were determined in 90 bladder cancer patients and 40 healthy controls using an enzyme linked immunosorbent assay. Preoperative serum MMP-7 and MMP-9 levels were significantly higher in cancer patients than control groups (p<0.001). In contast, serum TIMP-1 levels were lower (p<0.001). Alteration in MMP-7, and MMP-9, and TIMP-1 production may contribute to tumor angiogenesis and be associated with clinic-pathological features.

• Journal of Nutrition and Health
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• v.39 no.8
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• pp.756-761
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• 2006

Curcumin has been known for its anti-proliferative and apoptotic effects on several cancer cells. We examined the inhibitory effects of curcumin on cancer cell adhesion, motility, invasion and matrix metalloproteinase-9 (MMP-9) activity in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured with 0, 5, 10 or $20{\mu}M$ of curcumin. Curcumin significantly inhibited the adhesion of cancer cells to the fibronectin at $20{\mu}M$ and suppressed the motility and invasion of cancer cells at all concentrations. Also, the MMP-9 activity was inhibited by curcumin, but MMP-9 protein amounts were not affected. Our data indicate that curcumin inhibits motility, invasion and MMP-9 activity of MDA-MB-231 cells. Therefore, curcumin may contribute to the potential beneficial food component to prevent the cancer metastasis in human breast cancer.

• Animal cells and systems
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• v.10 no.2
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• pp.79-83
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• 2006

Tissue plasminogen activator (tPA) is used to lyse clots and reperfuse brain in ischemic stroke. However, sideeffects of intracerebral hemorrhage (ICH) and edema limit their clinical application. In part, these phenomena has been linked with elevations in matrix metalloproteinase-9 (MMP-9) in neurovascular unit. However little is known about their regulatory signaling pathways in brain cells. Here, I examine the role of MAP kinase pathways in tPA-induced MMP-9 regulation in rat cortical astrocytes. tPA $(1-10\;{\mu}g/ml)$ induced dose-dependent elevations in MMP-9 and MMP-2 in conditioned media. Although tPA increased phosphorylation in two MAP kinases (ERK, JNK), only inhibition of the JNK pathway by the JNK inhibitor SP600126 significantly reduced MMP-9 upregulation. Neither ERK inhibition with U0126 nor p38 inhibition with SB203580 had any significant effects. Taken together, these results suggest that c-jun N-terminal kinase (JNK) plays an essential role for tPA-induced MMP-9 upregulation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.6
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• pp.636-642
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• 2007

Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7393-7400
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• 2015

Matrix metalloproteinase (MMP) 9, a key member of multifunctional family of zinc dependent endopeptidases has been found to be upregulated during inflammation and in some cancers. MMPs cleave extracellular matrix (ECM) proteins and play critical roles in cellular apoptosis, angiogenesis, tumor growth and metastasis. Several genetic polymorphisms have been identified that show allele specific effects on MMP9 regulation and are associated with gastric cancer, the fourth most common malignancy in the world. Besides Helicobacter pylori infection, genetic predisposition is another documented risk factor for gastric carcinoma. The single nucleotide polymorphism (SNP) at position -1562C/T of MMP9 results in the modulation for binding of transcription factors to the MMP9 gene promoter and thereby causes differences in protein expression and enzymatic activity. MMP9 transcriptional regulation during gastric cancer development remains poorly known although several studies have demonstrated associations between MMP9 -1562 C/T polymorphism with different diseases. Knowledge on mechanisms of MMP9 upregulation during gastric cancer may provide new paradigm in diagnostics and therapeutics.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5055-5060
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• 2013

Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. Methods:Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopatholgic features and to patients' outcome. Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.

• Journal of Periodontal and Implant Science
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• v.43 no.1
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• pp.24-29
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• 2013

Purpose: Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, and they are inducible enzymes depending on an inflammatory environment such as periodontitis and bacterial infection in periodontal tissue. Gingival inflammation has been postulated to be correlated with the production of MMP-2 and MMP-9. The objective of this study was to quantify the expression and activity of MMP-9 and -2, and to determine the correlation between activity and expression of these MMPs in human gingival tissues with periodontitis. Methods: The gingival tissues of 13 patients were homogenized in $500{\mu}L$ of phosphate buffered saline with a protease inhibitor cocktail. The expression and activity of MMP-2 and -9 were measured by enzyme-linked immunosorbent assay and Western blot analysis, and quantified by a densitometer. For the correlation line, statistical analysis was performed using the Systat software package. Results: MMP-9 was highly expressed in all gingival tissue samples, whereas MMP-2 was underexpressed compared with MMP-9. MMP-9 activity increased together with the MMP-9 expression level, with a positive correlation (r=0.793, P=0.01). The correlation was not observed in MMP-2. Conclusions: The expression of MMP-2 and -9 might contribute to periodontal physiological and pathological processes, and the degree of MMP-9 expression and activity are predictive indicators relevant to the progression of periodontitis.

• Analytical Science and Technology
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• v.18 no.3
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• pp.188-193
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• 2005

Three different oriental natural plants (Angelicae Dahuricae Radix, Sanguisorba Officinalis L, Euonymus alatus) were extracted with 70% methanol under refluxing for 4 hr in order to investigate their inhibitory effect on Matrix Metalloproteinase-9 (MMP-9) by a modified gelatin zymography, where only euonymus alatus showed the inhibitory effect on the activity of Matrix MMP-9. The fraction was collected by using the mixture of ethyl acetate and hexane on silica gel column. Seven portions were obtained and three fractions of them (first, third and forth) showed inhibitory effect on the zymography. To verify the effect of these substances on cells, human hepatoma, Hep3B cells as a cancer model, and Chang liver cells as a normal model were selected. In order to examine the cell viability, $1{\mu}g/mL$ of each extract was treated on cells. Most of the methanol soluble fractions showed negligible toxicity on human liver cell line.

• 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.

• Nutritional Sciences
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• v.9 no.3
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• pp.145-151
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• 2006

Matrix metalloproteinases (MMP) play an important role in the extracellular matrix (ECM) degradation undetphysiological and pathological conditions. The present study examined the influence of (-)epigallocatechin gallate and quercetin on phorbol-12-myristate 13-acetate (PMA)-induced secretion of MMP-2 and MMP-9, when human umbilical vein endothelial cells (HUVEC) were treated with (-)epigallocatechin gallate and quercetin at supraphysiological concentrations of $25{\mu}mol/L$. No cytotoxicity was observed by MIT assay in response to a treatment with PMA in the presence of (-)epigallocatechin gallate and quercetin. Western blot analysis and gelatin zymography revealed that exposure of HUVEC to PMA enhanced the levels and gelatinolytic activities of pro and active forms of MMP-2 and active form of MMP-9. (-)Epigallocatechin gallate attenuated PMA-stimulated secretion of active forms of MMP-2 and MMP-9 concomitantly with a loss of activities of these enzymes, which was related to the decreased mRNA levels of MMP. Quercetin was more potent than (-)epigallocatechin gallate in alleviating MMP-9 protein secretion and activity with a decrease in MMP-9 mRNA accumulation. Taken together, the results indicated that (-)epigallocatechin gallte and quercetin exhibited inhibitory effects on MMP activity and may qualify as chemopreventive and cardiovascular protective agents.