• Title, Summary, Keyword: MMP-3

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Anti-Metastatic Activity of Juniperus chinensis Extract by Galectin-3 Inhibition (향나무 추출물의 Galectin-3 저해에 의한 암 전이 억제 효과)

  • Lee, Keyong Ho;Rhee, Ki-Hyeong
    • 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.

Effect of ganglioside GD3 synthase gene expression on VSMC proliferation via ERK1/2 pathway, cell cycle progression and MMP-9 expression

  • Lee, Young-Choon;Kim, Cheorl-Ho
    • Proceedings of the Korean Society of Plant Biotechnology Conference
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    • pp.81-90
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    • 2004
  • Sialic acid containing glycosphingolipids (gangliosides) have been implicated in the regulation of various biological phenomena such as atherosclerosis. Recent report suggeststhat exogenously supplied disialoganglioside (GD3) serves a dual role in vascular smooth muscle cells (VSMC) proliferation and apoptosis. However, the role of the GD3 synthase gene in VSMC responses has not yet been elucidated. To determine whether a ganglioside is able to modulate VSMC growth. the effect of overexpression of the GD3 synthase gene on DNA synthesis was examined. The results show that the overexpression of this gene has a potent inhibitory effect on DNA synthesis and ERK phosphorylation in cultured VSMC in the presence of PDGF. The suppression of the GD3 synthase gene was correlated with the down-regulation of cyclinE/CDK2. the up-regulation of the CDK inhibitor p21 and blocking of the p27 inhibition,whereas up-regulation of p53 as the result of GD3 synthase gene expression was not observed. Consistently, blockade of GD3 function with anti-GD3 antibody reversed VSMC proliferation and cell cycle proteins. The expression of the CD3 synthase gene also led to the inhibition of TNF--induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, GD3 synthase gene expression strongly decreased MMP-9 promoteractivlty in response to TNF-. This inhibition was characterized by the down-regulation of MMP-9,which was Iranscriptionally regulated at NF-B and activation protein-1 (AP-1) sites in the MMP-9promoter Finally, the overexpression of MMP-9 in GD3 synthase transfectant cells rescued VSMC proliferation. However MMP-2 overexpression was not affected the cell proliferation. These findings suggest that the fl13 synthase gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis.

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IMMUNOHISTOCHEMICAL STUDY ON EXPRESSION OF MMP-2 AND MMP-9 IN IRRITATION FIBROMA, ORAL LEUKOPLAKIA AND ORAL SQUAMOUS CELL CARCINOMA (자극성 섬유종, 구강백반증 및 구강편평세포암종에서 MMP-2 및 MMP-9 발현에 대한 면역조직화학적 연구)

  • Kim, Moon-Key;Lee, Eun-Ha;Kim, Jin;Lee, Eui-Woong;Cha, In-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.4
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    • pp.352-359
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    • 2006
  • MMP-2 and MMP-9, type IV collagenases which degrade basement membrane, have been known to play important roles in invasion and metastasis of tumor cells, In addition, they seem to be involved in cell differentiation, apoptosis, angiogenesis and immunity, etc. We immunohistochemically examined epithelial and stromal expressions of MMP-2 and MMP-9 in irritation fibroma, oral leukoplakia, and oral squamous cell carcinoma (OSCC) and have some results as follows: 1. Irritation fibromas, oral leukoplakias and OSCCs mostly showed increased expression of MMP-2 and MMP-9 in the epithelium and connective tissue compared with normal mucosa. 2. There was a significant difference in the epithelial expression of MMP-2 and MMP-9 between irritation fibroma and oral leukoplakia. 3. There was a significant difference in the epithelial and stromal expression of MMP-2 and MMP-9 between irritation fibroma and OSCC. 4. There was a significant difference in the stromal expression of MMP-9 between oral leukoplakia and OSCC. We concluded that rritation fibroma, oral leukoplakia and OSCC have somewhat different characteristics of MMP-2 and MMP-9 expressions, which perhaps result from different pathogenesis.

Sulfuretin Inhibits Ultraviolet B-induced MMP Expression in Human Dermal Fibroblasts

  • So, Hong-Seob;Kim, Seung-Hoon;Lee, Young-Rae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.3
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    • pp.533-539
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    • 2011
  • Sulfuretin is one of the main flavonoids produced by Rhusverniciflua. Sulfuretin has been shown to exhibit many pharmacological activities including anti-oxidant, anti-obesity, anti-inflammatory and anti-mutagenic activities. However, the anti-skin photoaging effects of sulfuretin has not yet been reported. In the present study, we investigated the inhibitory effect of sulfuretin on the expression levels of MMP-1 and -3 in the human dermal fibroblast cells. Western blot analysis and real-time PCR revealed sulfuretin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB-induced MAPK/NF-${\kappa}B$/p50 activation and MMP expression were completely blocked by pretreatment of sulfuretin. Taken together, sulfuretin could prevent UVB-induced MMP expressions through inhibition of MAPK/NF-${\kappa}B$/p50 activation.

Anti-invasion Effects of Calystegia soldanella Solvent Extracts and Partitioned Fractions on PMA-stimulated Fibrosarcoma Cells (갯메꽃 추출물과 유기용매 분획물의 암전이 억제 효과)

  • Son, Jaemin;Kim, Junse;Kim, Hojun;Seo, Youngwan
    • Journal of Life Science
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    • v.29 no.3
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    • pp.287-294
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    • 2019
  • Calystegia soldanella is distributed in coastal sand dunes and has high environmental adaptability; it is also known to be effective for anti-oxidant, anti-pyretic, anti-septic, and diuretic action. This study investigated the effect of crude extracts and organic solvent fractions of C. soldanella on MMP-2 and MMP-9 expression, MMP activity, and cell mobility in phorbol-12-myristate-13-acetate (PMA)-induced fibrosarcoma HT-1080 cells. C. soldanella was twice extracted, once with methylene chloride (MC) and once with methanol (MeOH). After the MC and MeOH extracts were combined, their suppressive effects on MMP-2 and MMP-9 expression, MMP enzymatic activity, and gene and protein expression were measured by gelatin zymography, enzyme-linked immunosorbent assay, reverse-transcription polymerase chain reaction, and western blot method. Cell mobility for the HT-1080 cells was observed by wound healing assay. The combined crude extracts showed a significant suppressive effects on MMP-2 and MMP-9 expression. To explore active inhibitory elements, the combined extracts were fractionated according to polarity into with n-hexane, 85% aqueous methanol, n-butanol, and water. Across these four solvent fractions, MMP-2 and MMP-9 activity and cell mobility in the HT-1080 cells were all strongly inhibited by the n-hexane fraction. These results suggest that C. soldanella extract and organic solvent fractions could be used as potent MMP inhibitors for effective anti-cancer treatments to suppress cancer invasion and metastasis.

Expression Analysis of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases from In Vitro Maturation Oocytes Complexes in Porcine (돼지 체외성숙난자에서 MMPs와 TIMPs의 발현 분석)

  • Kim, Sang-Hwan;Kang, Hyun-Ah;Kim, Dae-Seung;Lee, Myeong-Seop;Seo, Kang-Suk;Min, Kwan-Sik;Yoon, Jong-Taek
    • Reproductive and Developmental Biology
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    • v.34 no.1
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    • pp.55-62
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    • 2010
  • Matrix metalloproteinases (MMP) play important roles in extracellular matrix (ECM) remodeling during ovarian follicular development, oocytes development and ovulation. In an attempt to investigate the effect of MMP activation in development cumulus-oocytes complexes, we examined the localization and expression of MMP, and monitored MMP expression profile. Cumulus-oocytes complexes were collected and matured in vitro for 24 hr, 36 hr and 48 hr. A mRNA expression of MMP-2, MMP-9, TIMP-2 and TIMP-3 was detected in all culture medium regardless of CC, DC and CDCs. Activity of MMP-2 in the DC progressively was increased from 24 hr to 48 hr. But MMP-9 was not detected in all culture medium. The localization of MMP-2 was also measured by immunohistochemistry analysis. The MMP-2 and TIMP-2 was detected in cumulus cell and oocyte zone pellucida. Expression of MMP-2 protein in the COCs was progressively increased from 24 hr to 48 hr. However, MMP-9 protein was progressively decreased from 24 hr to 48 hr. And TIMP-2 protein was most highly expressed in the CDCs 36 hr. Expression of TIMP-3 protein in the CDCs was progressively increased from 24 hr to 48 hr. In conclusion, these results suggest that MMP-2 plays a role in maintaining normal maturation and development by controlling the ECM inhibitor concentration on cumulus cell and oocytes.

MMP and TIMP production in periodontal ligament fibroblasts stimulated by Prevotella nigrescens lipopolysaccharide (Prevotella nigrescens lipopolysaccharide로 자극한 치주인대 섬유아세포에서 기질금속단백분해효소와 단백분해효소억제제의 생성 양상에 대한 연구)

  • Yang, Won-Kyung;Lee, Woo-Cheol;Kim, Mi-Ri;Son, Ho-Hyun
    • Restorative Dentistry and Endodontics
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    • v.30 no.5
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    • pp.372-384
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    • 2005
  • The purpose of this study was to monitor the secretion of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) by human periodontal ligament (PDL) fibroblasts stimulated with Prevotella nigrescens lipopolysaccharide (LPS), and to examine the effect of calcium hydroxide treatment on P. nigrescens LPS. LPS was extracted and purified from anaerobically cultured P. nigrescens. PDL fibroblasts were stimulated by the LPS (0, 0.1, 1, 10 ${\mu}g/ml$) or LPS (10 ${\mu}g/ml$) pretreated with 12.5 mg/ml of $Ca(OH)_2$ for 3 days, for various periods of time (12, 24, 48 h). Immunoprecipitation were performed for protein level analysis of MMP-1 MMP-2 and TIMP-1. Total RNA was isolated and real-time quantitative polymerase chain reaction (PCR) was performed for quantification of MMP-1 mRNA. According to this study, the results were as follows: 1. The p개duction of MMP-1 by stimulation with P. nigrescens LPS increased in time-dependent manner, and showed maximum value at 48 h in both protein and mRNA level. But there was no dose-dependent increas. 2. MMP-2 production time-dependently increased when stimulated with 1 and 10 ${\mu}g/ml$LPS, but there was no dose-dependent increase. 3. TIMP-1 p개duction increased to 24 h, but decreased at 48 h. It increased when stimulated with 0.1 and 1${\mu}g/ml$, but suppressed at 10 ${\mu}g/ml$ .4. P. nigrescens LPS pretreated with $Ca(OH)_2$ markedly downregulated MMP-1 gene expression.

Effect of Antioxidation and Inhibition of Matrix Metalloproteinase-1 from Ligularia fischeri (곰취의 항산화와 UVA에 의한 MMP-1 발현 저해효과)

  • Na, Young;Kim, Jin-Hwa;Sim, Gwan-Sub;Lee, Bum-Chun;Pyo, Hyeong-Bae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.32 no.3
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    • pp.129-134
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    • 2006
  • In this study, we examined the effects of antioxidant, lipid peroxidation inhibition and suppression of UVA-induced MMP-1 expression in human dermal fibroblasts. Ligularia fischeri extract showed free radical scavenging effect by 82.3% at 5 mg/mL and superoxide radical scavenging effect by 79.3% at 5 mg/mL in the kanthine/xanthine oxidase system, respectively. At the concentration of $500{\mu}g/mL$, L. fischeri extract showed 97% inhibition on lipid peroxidation of linoleic acid. UVA induced MMP expression in human dermal fibroblasts was reduced 35% by treatment with $100{\mu}g/mL$ of L. fischeri extract. These results suggest that L. fischeri extract can be used for an anti-aging agent by antioxidation, lipid peroxidation inhibition and reducing UVA-induced MMP-1 production.

Quantitative Real-Time RT-PCR of ITGA7, SVEP1, TNS1, LPHN3, SEMA3G, KLB and MMP13 mRNA Expression in Breast Cancer

  • Kotepui, Manas;Thawornkuno, Charin;Chavalitshewinkoon-Petmitr, Porntip;Punyarit, Phaibul;Petmitr, Songsak
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5879-5882
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    • 2012
  • Breast cancer is the leading cause of cancer deaths among women worldwide, including Thailand. In the present study, the differential mRNA expression of SVEP1, LPHN3, KLB, ITGA7, SEMA3G, TNS1 and MMP13 genes was examined in breast cancer using quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR). Among these genes, increased LPHN3 and MMP13 mRNA expression levels correlated with axillary-node metastasis (P=0.02). Multiple logistic regression analysis revealed that LPHN3 and MMP13 mRNA expression is significantly associated with axillary node status in breast cancer (P=0.04).

Serum Level of MMP-3 in Patients with Oral Squamous Cell Carcinoma - Lack of Association with Clinico-pathological Features

  • Tadbir, Azadeh Andisheh;Purshahidi, Sara;Ebrahimi, Hooman;Khademi, Bijan;Malekzadeh, Mahzad;Mardani, Maryam;Taghva, Masumeh;Sardari, Yasaman
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4545-4548
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    • 2012
  • Background: MMP-3 is a proteolytic enzyme of the matrix metalloproteinase family. Protein degradation which is their fundamental action regulates different activities of tumor cell such as their growth, differentiation, apoptosis, migration, invasion, angiogenesis as well as their resistance to the immune system. Aim: The aim of this study was to determine MMP-3 serum levels in patients with OSCC and investigate if they correlate with clinicopathological features. Method and materials: Using an ELISA kit, we assessed and compared the circulating levels of MMP-3 in blood serum of 45 oral squamous cell carcinoma patients with 45 healthy control samples. Results: The serum MMP-3 level in OSCC patients was significantly higher ($9.45{\pm}4.6$ ng/ml) than healthy controls ($5.9{\pm}3.6$ ng/ml, p<0.001), especially in females and in older patients. However, there was no apparent correlation in serum MMP-3 concentration with the clinico-pathological features such as tumor location, stage, tumor size, nodal status, distant metastasis, histological grade and smoking. Discussion: This result suggests that the measurement of serum MMP-3 concentration might be helpful to diagnose OSCC but not to predict prognosis.