• Perinatology
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• v.29 no.4
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• pp.170-174
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• 2018

Objective: Progesterone is used to prevent recurrent preterm delivery, however the molecular mechanisms of its effect are incompletely understood. The objective of this study was to determine the effect of progesterone on tumor necrosis factor $(TNF)-{\alpha}$-induced matrix metalloproteinase (MMP)-9 activity in human choriodecidual (CD) membranes. Methods: We collected CD membranes from women with uncomplicated term pregnancies who were scheduled for elective cesarean delivery (n=10). CD membranes ($1{\times}1cm$) were incubated in tissue culture media at $37^{\circ}C$. We pre-treated the CD membranes with progesterone (P4), $17{\alpha}$-hydroxyprogesterone caproate (17P), promegestone (R5020), or vehicle (ethanol) for 24 hours. The CD membranes were subsequently treated with $TNF-{\alpha}$ (with continued progesterone treatment) for 48 hours, then media was harvested for measuring MMP-9 activity by zymography and total protein was isolated from CD membrane tissues for MMP-9 expression by western blot analysis. Results: P4, 17P, and R5020 significantly reduced $TNF-{\alpha}$-induced MMP-9 activity in fetal membrane tissue samples (P=0.0078, P=0.0156, and P=0.0391, respectively) by zymography. Western blot analysis also showed decreased expression of MMP-9 in progesterone pretreated groups (P=0.0313). Conclusion: Progesterone reduces $TNF-{\alpha}$-induced MMP-9 activity in human CD membranes. These findings may provide further support for the role of progesterone in preventing preterm birth.

• The Korean Journal of Mycology
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• v.45 no.3
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• pp.175-187
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• 2017

Laetiporus sulphrueus var. miniatus is widely distributed worldwide, and has commonly been used as a medicinal mushroom. In the present study, we investigated the effects of water extract and solvent fractions from the Laetiporus miniatus as possible antioxidant, anti-thrombin and anti-invasive agents against phorbol 12-myristate 13-acetate (PMA)- or thrombin-induced matrix metalloproteinase-2 (MMP-2) and MMP-9 activities. Samples were fractionated into n-hexane, $CHCl_3$, ethyl acetate, n-butanol, and water fractions, and individually analysed. The water fraction had the highest extraction yield at 34.90% (w/w), while the n-butanol fraction demonstrated the highest anti-oxidative activity at 81.44%. In the thrombin inhibitory activity test, the water fraction exhibited the highest activity at 94.64%. Even at the concentration of $40{\mu}g/mL$, evaluation of anti-proliferating activity in YD-10B cells did not reveal any cytotoxic effects. Although MMP-9 expression in YD-10B cells increased after the addition of PMA and thrombin, MMP-2 did not. Additionally, MMP-2/-9 levels in PMA-treated YD-10B cells (i.e., both mRNA expression and protein activation) were highly inhibited in the hexane and chloroform fractions. Compared with MMP-2 levels, MMP-9 mRNA expression and proteolytic activity were inhibited to a greater extent by the hexane and chloroform fractions in thrombin-treated YD-10B cells. Taken together, these results support that thrombin induces tumor invasion through MMP-2/9 and suggest that the L. miniatus may act as an effective functional food, conferring anti-oxidative, anti-thrombotic and anti-cancer activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1470-1474
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• 2008

This study was performed to examine the anti-metastatic effect of ethanol extract of Samguikoeui-Tang (SGKE), a formula consisting of four oriental herbs, in highly-metastatic HT1080 human fibrosarcoma cells. SGKE significantly inhibited the adhesion of HT1080 cells to matrigel at nontoxic concentrations in a dose-dependent manner, while it did not exert cytotoxicity against HT1080 cells up to the concentration of 100 ${\mu}g$/ml. Also, SGKE depressed the activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) by gelatin zymography. However, SGKE did not affect the mRNA expression of MMP-2 and TIMP-2, an inhibitor of MMP-2, by RT-PCR analysis. In addition, the effect of SGKE on HT1080 cell invasion was determined using Boyden chamber assay. SGKE suppressed the invasion of HT1080 cells in a dose-dependent manner. Taken together, these results suggest that SGKE has an anti-metastatic effect via inhibition of MMP-2 and -9 activities.

• BMB Reports
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• v.50 no.12
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• pp.628-633
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• 2017

Gastrin-releasing peptide (GRP) has been reported to be implicated in the pathogenesis of inflammatory disorders. The migration and proliferation of vascular smooth muscle cells (VSMCs) are key components of vascular inflammation that leads to the development of atherosclerosis. The present study aimed to investigate the molecular effect of GRP on VSMC proliferation and migration. We report that GRP significantly enhanced the proliferation and migration of rat VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase-2 and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the activation of the signal transducer and activator of transcription-3 (STAT3). In addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via STAT3 activation.

• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.82-89
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• 2006

Background: Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix, which is an important step in tumor invasion and metastasis. A positive correlation between the expression of MMP-9 and aggressive behavior of renal cell carcinomas (RCCs) has been reported. MMP-9 expression in RCCs and adjacent normal kidney tissues were examined in this study. Materials and Methods: Twenty-five patients pathologically diagnosed as clear cell RCCs, from specimens obtained at radical nephrectomy, between May 2003 and December 2004 were enrolled in this study. MMP-9 activity was estimated using gelatin zymography, and quantified using a laser densitometer. The results were compared with clinicopathological characteristics. Results: The expression of MMP-9 was significantly elevated in the RCC compared with non-tumor kidney specimens (p<0.01). The levels of MMP-9 expression in the RCC patients with large tumors (>4 cm) or vascular invasion were significantly higher than in those without these clinical manifestations (p<0.01). There were also significant differences in the expression of MMP-9 among T stages (p<0.01). The tissue MMP-9 level was the highest in nuclear grade 4, but there was no statistical significance between the histological grades (p=0.17). Conclusions: These results suggest that enhanced MMP-9 expression contributes to carcinogenesis and tumor progression in the later stages of RCC.

• 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.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.510-518
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• 2010

Purpose : Kawasaki disease (KD) is a systemic vasculitis, a leading cause of pediatric acquired heart disease. Histopathological findings of coronary artery lesion (CAL) in KD indicate destruction of the coronary artery wall with diffuse vasculitis. Matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) might play central roles in this process. Special attention to MMP-9 has recently been emerging. This study was performed to investigate the clinical significance of MMP-9 and its inhibitors, TIMP-1 and TIMP-2, in KD. Methods : We compared 47 KD patients with 14 febrile controls. Serum MMP-9 and TIMP-1, TIMP-2 were measured by ELISA and compared according to clinical stages and coronary involvement. Results : In acute stage, MMP-9 and TIMP-1 were significantly higher, whereas TIMP-2 was lower, in KD than those in febrile controls ($P$<0.05). The elevated MMP-9 levels in acute phase significantly decreased during the subacute and convalescent phases ($P$<0.05). During acute phase, the MMP-9, TIMP-1, and MMP-9/TIMP-2 levels in the CAL group were lower than those in the non-CAL group, but they increased significantly in the subacute phase ($P$<0.05). MMP-9 has a positive correlation with TIMP-1 in the acute and subacute phases, and negative correlation with TIMP-2 in the subacute and convalescent phases ($P$<0.05). Conclusion : These results suggest that MMP-9, TIMP-1, and the imbalance in MMP-9 and TIMP-2 might play important roles on the pathophysiology of KD and especially on the development of CAL. However, further larger studies are needed.

• Journal of Life Science
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• v.24 no.6
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• pp.700-706
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• 2014

Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1049-1052
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• 2012

The purpose of this study was to evaluate expression and prognostic value of matrix metalloproteinase-7 (MMP-7) in colorectal cancer (CRC) patients. CRC tissues and corresponding distal normal mucosa tissues of 118 CRC patients were assessed by immunohistochemistry. Correlations between MMP-7 expression, patients' clinic pathological features, and overall survival rate were analyzed. We found that positive expression of MMP-7 in CRC tissues was significantly higher than that in distal normal mucosa (61.0% vs. 39.8%, p =0.001). Poor histological differentiation, advanced clinical stage and lymph node metastasis were significantly correlated with MMP-7 expression in CRC. The overall survival rate was significantly higher in the MMP-7 negative group than the positive group (Log-rank test= 9.957, p= 0.002). MMP-7 appeared as a significant independent prognostic factor through multivariate survival analysis. Collectively, we found MMP-7 expression to be correlated with progression and metastasis of CRC and thus could be used as a predictive marker of prognosis in CRC patients.

• Journal of Life Science
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• v.23 no.3
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• pp.355-360
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• 2013

Withaferin A is an active component of Withania somnifera, and has anti-inflammatory, anti-tumor, and immune modulatory effects. However, the effects of withaferin A on metalloproteinase (MMP)-9 expression and activity have not been investigated. In this study, we investigated the ability of withaferin A to inhibit MMP-9 expression and activity in PMA-treated human cervical carcinoma Caski cells. Withaferin A markedly inhibited the PMA-induced MMP-9 activity in a dose-dependent manner. Withaferin A decreased not only PMA-induced MMP-9 promoter activity but also PMA-mediated MMP-9 mRNA and protein expression in Caski cells. NF-${\kappa}B$ promoter activity, which is important in MMP-9 expression, was also decreased in combined treatment with withaferin A and PMA. Furthermore, withaferin A markedly suppressed the ability of PMA-mediated migration in Caski cells. Our findings suggest that withaferin A might inhibit PMA-induced migration through the down-regulation of MMP-9 expression and activity.