• Title, Summary, Keyword: MMP-9

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Effect of Allergen Removed Rhus Verniciflua Extract on Inhibition of Tumor Metastasis (알러젠 제거 옻나무 추출물이 종양 전이 억제에 미치는 영향)

  • Park, Jae-Hyun;Moon, Goo
    • Journal of Korean Traditional Oncology
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    • v.15 no.1
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    • pp.47-61
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    • 2010
  • Objective : The aim of this present study is to evaluate the inhibitory effect of allergen removed Rhus verniciflua (ARV) on Matrix Metalloproteinase-9 (MMP-9), Matrix Metalloproteinase-2 (MMP-2) which is considered to have a clinically important role in tumor metastasis. Methods : The inhibitory effects of standardized extract of ARV on the MMP-2, MMP-9 were investigated by spectrofluorometer while the inhibitory effects on the active MMP-2, pro MMP-2, pro MMP-9 were investigated by zymography. Antimetastatic effect of standardized extract of ARV was investigated in vitro on human fibrosarcoma cell (HT1080)'s invasion through Matrigel. Results : The standardized extract of ARV showed inhibitory effects on the active MMP-2 (IC50, $1.01{\mu}g$/ml), active MMP-9 (IC50, $2.5{\mu}g$/ml) depending on concentrations which was determined by spectrofluorometer. The standardized extract of ARV showed inhibitory effects on the active MMP-2, pro MMP-2, pro MMP-9 depending on concentrations which was determined by zymography. However its inhibitory effect on pro MMP-9 was relatively weaker rather than active MMP-2, pro MMP-2. The standardized extract of ARV showed inhibitory effects in vitro on human fibrosarcoma cell (HT1080)'s invasion through Matrigel according to concentration. Conclusions : These results indicate that standardized extract of ARV has antimetastatic effect through inhibit again MMP-2, MMP-9. Also its inhibitory effect is more powerful on active MMP-2, pro MMP-2 than on active MMP-9, pro MMP-9. It is necessary to conduct further studies on other MMP families, TIMP, and each component of standardized extract of ARV.

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Effect of Sulforaphane on LPS-Induced Matrix Metalloproteinase-9 (MMP-9) Expression (Sulfolaphane이 lipopolysaccharide (LPS)에 의해 유도된 matrix metalloproteinase-9 (MMP-9) 발현에 미치는 영향)

  • Lee, Jung-Tae;Woo, Kyung-Jin;Kwon, Taeg-Kyu
    • Journal of Life Science
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    • v.20 no.2
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    • pp.275-280
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    • 2010
  • Sulforaphane is a naturally occurring member of the iosothiocyanate family, which reveals chemopreventive capacities including anti-cancer, anti-inflammation and inhibition of MMP-9 activities. In this study, we investigated the effect of sulforaphane on the expression of matrix metalloproteinase-9 (MMP-9) in lipopolysaccharide (LPS)-induced Raw 264.7 cells. Sulforaphane strikingly suppressed the LPS-induced MMP-9 activity and mRNA expression in a dose-dependent manner. In addition, sulforaphane inhibited not only the LPS-induced MMP-9 promoter activity but also LPS-mediated activator protein-1 (AP-1) and nuclear factor-kB (NF-${\kappa}B$) promoter activity. Transient transfection by MMP-9 constructs, in which specific transcriptional factors were mutagenized, indicated that the effects of LPS and sulforaphane were mediated via AP-1 and NF-${\kappa}B$ response elements. We found that sulforaphane had the ability to suppress LPS-induced invasion in vitro. Taken together, these results demonstrated that sulforaphane effectively suppressed LPS-induced MMP-9 expression via modulation of promoter elements (AP-1 and NF-${\kappa}B$) in MMP-9 transcriptional activation.

Association of Matrix Metalloproteinase (MMP)-2 and -9 Expression with Extra-gastrointestinal Stromal Tumor Metastasis

  • Wang, Chao;Ma, Hong-Xi;Jin, Mei-Shan;Zou, Ya-Bin;Teng, Yong-Liang;Tian, Zhuang;Wang, Hai-Ying;Wang, Yin-Ping;Duan, Xiu-Mei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4187-4192
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    • 2014
  • Matrix metalloproteinase (MMP)-2 and MMP-9 are important proteases involved in invasion and metastasis of various tumors. Extra-gastrointestinal stromal tumors (EGISTs) are rare neoplasms. This study was performed to assess MMP-2 and MMP-9 expression in EGIST tissue samples for association with clinicopathological data from the patients. Twenty-one surgical EGIST tissue specimens were collected for analysis of MMP-2 and MMP-9 expression using immunohistochemistry. MMP-2 and MMP-9 proteins were expressed in all of the epithelial cell types of EGISTs, whereas they were only expressed in 75% of the spindle cell type, although there was no statistically significant difference (p>0.05). Expression of MMP-2 and MMP-9 proteins was associated with tumor size, mitotic rate, tumor necrosis, and distant metastasis (p<0.05). MMP-2 expression was linked with MMP-9 levels (p<0.05). However, there was no correlation between MMP-9 expression and age, sex, primary site, or cell morphology in any of these 21 EGIST patients (p>0.05). Moreover, expression of MMP-2 and MMP-9 proteins increased with the degree of EGIST risk. This study provided evidence of an association of MMP-2 and MMP-9 expression with advanced EGIST behavior.

MAP Kinase Activation is Required for the MMP-9 Induction by TNF-Stimulation

  • Kim, Kyung-Chan;Lee, Chu-Hee
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1257-1262
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    • 2005
  • MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-$\alpha$ stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-$\alpha$ stimulation. To investigate the signaling pathway underlined in TNF-$\alpha$ induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-$\alpha$ treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-$\alpha$. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-$\alpha$ induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-$\alpha$. Taken together, we found that TNF-$\alpha$ stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.

Withaferin A Inhibits PMA-Induced MMP-9 Expression in Human Cervical Carcinoma Caski Cells (인간 자궁경부암세포인 Caski세포에서 withaferin A에 의한 PMA 매개 matrix metalloproteinase-9의 발현 억제 효과)

  • Kim, Dong Eun
    • 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.

Inhibitory Effect of Naringenin on MMP-2, -9 Activity and Expression in HT-1080 Cells (HT1080 세포주에서 naringenin의 MMP-2, -9 효소 활성 및 발현 억제 효과)

  • Chae, Soo-Chul
    • Environmental health and toxicology
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    • v.24 no.1
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    • pp.63-70
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    • 2009
  • Naringenin, major one of the citrus flavonoids, have been identified that exert antioxidative, anticancer effects. The present study investigated the effects of naringenin on tumor invasion and matrix metalloproteinases(MMPs) activities. Naringenin inhibited cell invasion of HT-1080 fibrosarcoma cells in a dose-dependent manner. The activities of MMP-2 and MMP-9 were inhibited by naringenin as demonstrated by gelatin zymography assay. Furthermore, the amounts of MMP-2, MMP-9, and MT1-MMP mRNA were analyzed in the cells. MMP-2, MMP-9, and MT1-MMP mRNA expression were suppressed by naringenin with time and dose-dependent. These results demonstrate that anti-metastatic activities of naringenin resulted from blocking of invasion of the HT-1080 cells. Taken together, the results of this studies provide evidence that naringenin possess an anti-metastatic activity.

Serum Levels of MMP9 and MMP2 in Patients with Oral Squamous Cell Carcinoma

  • Lotfi, Alireza;Mohammadi, Ghodrat;Tavassoli, Atena;mousaviagdas, Mehrnoosh;Chavoshi, Hadi;Saniee, Lale
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.4
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    • pp.1327-1330
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    • 2015
  • Background: Squamous cell carcinoma (SCC) is the most common cancer in the oral area. Matrix metalloproteinases (MMPs) and especially MMP-2 and MMP-9 are increased in malignancy and lymph node involvement in oral SCCs. We aimed to evaluate the serum levels of MMP-2 and MMP-9 in patients with oral SCC compared to normal subjects and their relation with clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included and serum levels of MMP-2 and MMP-9 were compared between groups. Also, the correlation between these markers with clinicopathological findings including grade (T) and node (N) were evaluated. Results: Patients with oral SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p<0.001) compared to healthy subjects. With increase in grade T, MMP-2 was significantly increased (p=0.001), but in the MMP-9 case this was not significant (p=0.27). The levels of MMP-2 (p=0.002) and MMP-9 (p=0.01) in cases with lymph node involvement and that of MMP-2 in subjects with smoking history (p=0.001) were significantly high. There was significantly positive correlation between MMP-2 with grade T tumor (r=0.598, p=0.005), lymph node involvement (r=0.737, p<0.001) and smoking (r=0.674, p=0.001) and also between MMP-9 and lymph node involvement (r=0.474, p=0.03). Conclusions: Both markers are significantly increased in oral SCC compared to healthy subjects. However, MMP-2 was better for evaluating lymph node involvement and tumor grade.

Increased Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Levels in the Cerebrospinal Fluid from Children with Aseptic Meningitis (무균성 뇌수막염 소아에서 뇌척수액내 Matrix Metalloproteinase(MMP)-9과 Tissue Inhibitor of Metalloproteinase(TIMP)-1의 증가)

  • Yang, Ju Hee;Park, Min Hyuk;Shim, Jung-Yeon;Jung, Hye Lim;Park, Moon Soo;Keum, Dong Hyuck
    • Korean Journal of Pediatrics
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    • v.46 no.6
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    • pp.548-553
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    • 2003
  • Purpose : Matrix metalloproteinase(MMP)-9 is known to breakdown the blood-brain barrier by degrading the extracellular matrix of the subendothelial basement membrane in meningitis. Tissue inhibitor of metalloproteinase(TIMP)-1, a known inhibitor of MMP-9, has been postulated to inhibit the proteolytic activity of MMP-9 by bindng to MMP-9, but their interaction has not been fully understood yet. So far, there have been some reports on the relationship of MMP-9 and TIMP-1 in bacterial meningitis, but few reports in viral meningitis. Furthermore, there has been no report on this in Korea. We investigated the concentrations of MMP-9 and TIMP-1 in cerebrospinal fluid (CSF) and serum of patients with viral meningitis and control subjects, and evaluated their relationship with other clinical parameters of meningitis. Methods : CSF and blood were obtained from 25 subjects with viral meningitis and 14 control subjects. After centrifugation, supernatants were stored at $-20^{\circ}C$ and we assayed concentrations of MMP-9 and TIMP-1 by the sandwich ELISA method. Results : Concentrations of CSF MMP-9 and TIMP-1 were significantly elevated in patients with viral meningitis, when compared with those in control subjects. Their serum levels showed no differences between the two groups. MMP-9 levels were closely correlated with TIMP-1 levels in the CSF($r_s=0.42$, P<0.05). CSF MMP-9/TIMP-1 ratios were significantly higher in patients with viral meningitis than those in the control subjects(P<0.05). Both CSF MMP-9 and TIMP-1 levels positively correlated with CSF total leukocyte counts($r_s=0.43$, P<0.05, $r_s=0.48$, P<0.05). TIMP-1 levels positively correlated with total protein concentrations in the CSF($r_s=0.43$, P<0.05). Conclusion : MMP-9 and TIMP-1 may play an important role in the breakdown and maintenance of BBB in viral meningitis, respectively.

The Relationship Between Expression of Matrix Metalloproteinases(MMPs)-2, 9 and Tissue Inhibitors of Metalloproteinase(TIMPs)-1, 2 and Survival Time in Resected Non-Small Cell Lung Cancer (비소세포폐암에서 Matrix Metalloproteinase(MMPs)-2, 9와 Tissue Inhibitor of Metalloproteinase(TIMPs)-1, 2의 발현과 생존율과의 관계)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.453-462
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    • 2002
  • Background : Matrix metalloproteinases(MMPs) are a large family of proteolytic enzymes, which are involved in the degradation of many different components of the extracellular matrix. There is increasing evidence indicating that individual MMPs have important roles in tumor invasion by inactivating the MMPs. In this study, the correlation between MMPs and TIMPs expression, and the clinical outcome was investigated. Materials and Methods : Immunohistochemical staining of MMP-2, 9 and TIMP-1,2 were performed on paraffin-embedded tumor sections from 74 resected primary non-small cell lung cancers. Results : In 74 patients, MMP-2, MMP-9, TIMP-1, and TIMP-2 immunoreactivity was demonstrated in 24(34%), 19(26%) and 32(43%) of the paraffin-embedded tumors, respectively. The median survival of the MMP-2 positive cases was significantly shorter than that of the negative cases(20 vs 34 months). The median survival of the TIMP-2 positive cases was also was significantly longer than that of the negative cases (34 vs 18 months). The MMP-2, and MMP-9 expression level had a positively correlation with a more advanced stage and lymph node metastasis. There was inverse correlation between TIMP-2 expression and tumor invasion. The median survival of the MMP-2 negative/TIMP-2 positive cases was higher than that of the other cases. Conclusion : These results suggest that tumor invasion and lymph node metastasis are closely related to MMP-2 and MMP-9 expression. There was an inverse correlation between TIMP-2 and MMP-9 expression, and tumor invasion.

Extract of Moringa Root Inhibits PMA-induced Invasion of Breast Cancer Cells (유방암 세포주에서 PMA로 유도된 암세포 침투에 대한 모링가 뿌리 추출물의 억제효과)

  • Cho, Hyun-Ji;Chang, Young-Chae
    • Journal of Life Science
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    • v.24 no.1
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    • pp.8-13
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    • 2014
  • The moringa (Moringa oleifera Lam.) plant is used as food and as an anti-allergic agent. In this study, we studied the inhibitory effect of moringa root extract on the expression of PMA-induced matrix metalloproteinase-9 (MMP-9), which is the main factor implicated in the invasion and metastasis of cancer cells in MCF-7 cells. At first, various moringa extracts were examined in the MCF-7 cells. Both moringa root extract and leaf extracts inhibited PMA-induced MMP-9 activity, but the root extract suppressed PMA-induced MMP-9 activity to a greater extent than the leaf extract. The moringa root extract also inhibited PMA-induced MMP-9 protein expression and cell invasion. According to RT-PCR, the treatment of the MCF-7 cells with moringa root extract decreased levels of PMA-induced MMP-9 mRNA expression, but not the expression of TIMP-1 and -2, indicating that moringa root extract prevents the transcription of MMP-9 in response to PMA. In addition, moringa root extract specifically suppressed the phosphorylation of ERK/JNK, but not p38. We suggest that moringa root extract abolishes MMP-9 activity/expression through ERK/JNK. In conclusion, moringa root extract suppressed PMA-induced MMP-9 activity/expression by inhibiting the phosphorylation of ERK/JNK in MCF-7 cells. These results indicate that moringa root extract may be a potential antimetastatic and anti-invasive agent. Future clinical research is needed on the anticancer properties of moringa root extract.