• Fisheries and Aquatic Sciences
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• 제21권6호
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• pp.16.1-16.7
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• 2018

Background: Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content. Methods: In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells. S. horneri crude extract was fractionated with organic solvents, namely, water ($H_2O$), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solvent-partitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting. Results: All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography. Except $H_2O$ fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Conclusion: Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules.

• 대한치과교정학회지
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• 제36권2호
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• pp.91-102
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• 2006

이 연구는 치낭과 그 주위 조직 세포에서 matrix metalloproteinase (MMP)-3과 -9의 발현에 대한 인도메타신의 영향을 관찰하여 인도메타신이 치아의 맹출에 미치는 영향의 일단을 규명하기 위해 시행되었다. 생후 10-12주된 10마리의 개를 실험군 8마리와 대조군 2마리로 나누고 실험군은 인도메타신을 체중에 대하여 통상적 복용량인 인도메타신 2 mg/Kg/day을 7일간 및 14일간 투여한 군과 과량의 8 mg/Kg/day을 7일간 및 14일간 투여한 군으로 나누고 대조군은 빈 캅셀을 placebo로 투여한 후 희생하고 맹출 중인 영구치 치배를 적출하여 조직 처리하고 H-E 염색 및 MMP-3과 -9에 대한 면븐염색 시행 후 광학현미경으로 검경하였다. 관찰결과 대조군에서는 파골세포, 조골세포, 치주인대 세포, 법랑모세포 및 상아모세포에서 모두 MMP-3과 -9의 발현이 뚜렷하게 관찰되었다. 대조군에 비해 인도메타신 투여군에서 파골세포, 조골세포, 치주인대 세포는 MMP-3과 -9의 발현이 억제된 소견이 관찰되었으며 인도메타신의 투여기간이 길수록 투여량이 많을수록 더 뚜렷하게 관찰되었다. 법랑모세포와 상아모세포는 대조군과 실험군의 MMP-3과 -9의 발현의 차이가 관찰되지 않았다. 이상의 결과에 의하면 prostaglandin (PG) 생합성 억제제인 인도메타신은 치낭의 파골세포, 조골세포 및 치주인대 세포에서 MhfP-3과 -9의 발현을 억제하였으며 이는 인도메타신 투여로 치아 맹출이 억제될 수 있음을 시사한다.

• BMB Reports
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• 제46권11호
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• pp.533-538
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• 2013

The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy- 3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-${\kappa}B$ activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4107-4113
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• 2013

Objective: Matrix metalloproteinase-9(MMP-9) plays an important role in tumor cell invasion. Although it has been studied frequently in ovarian cancer, its prognostic impact is still equivocal. The aim of this study was to more precisely estimate its prognostic significance. Method:We searched Pubmed, Embase, OVID, Sciencedirect and CBM databases to identify eligible studies. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were pooled across studies using fixed-effects or random-effects models. We also performed subgroup analysis. Results: 30 studies (n=2552 patients) focusing on prognosis or expression of MM-9 were included. Increased expression of MMP-9 was associated with poor prognosis in ovarian cancer patients (HR=1.68, 95%CI 1.09-2.59, p=0.02). Besides, MMP-9 expression in ovarian cancer was significantly higher than non-malignant tumors (OR=11.46, 95%CI 8.47-15.50, P<0.00001). Moreover, increased expression of MMP-9 was significantly associated with FIGO stage (OR=4.85, 95%CI 2.60-9.04, P<0.00001), grade of differentiation (OR=3.34, 95%CI 2.46-4.54, P<0.00001), lymph node metastasis (OR=5.75, 95%CI 3.71-8.92, P<0.00001) and there was no association with histological type of ovarian cancer. Conclusions: Increased expression of MMP-9 was associated with poor prognosis in ovarian cancer patients. Down-regulation of MMP-9 is an attractive therapeutic approach which might improve outcome of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3507-3511
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• 2012

Objective: The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion and metastasis of breast cancer cells by RNA interference. Methods: LOX-RNAi-LV was designed, synthesized, and then transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 was determined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasiveness were assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal breast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry. Results: Expression of LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB-231 cells. Migration and invasion abilities were obviously inhibited. The expression of LOX protein in breast cancer, cancer-adjacent normal breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), respectively, associations being noted with clinical stage, lymph node metastasis, tumor size and ER, PR, HER2, but not age. LOX protein was positively correlated with MMP-2 and MMP-9. Conclusion: LOX displayed an important role in invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression which probably exerted synergistic effects on the extracellular matrix (ECM).

• Journal of Korean Neurosurgical Society
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• 제50권4호
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• pp.288-292
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• 2011

Objective : Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 have been known to play an important role in secondary inflammatory reaction after spinal cord injury (SCI). The aim of this study was to investigate the expression and activity of MMP-2 and MMP-9 and to determine their relationship with disruption of endothelial blood-barrier after photochemically induced SCI in rats. Methods : Female Sprague-Dawley rats, weighing between 250 and 300 g (aged 8 weeks) received focal spinal cord ischemia by photothrombosis using Rose Bengal. Expressions and activities of MMP-2 and MMP-9 were assessed by Western blot and gelatin zymography at various times from 6 h to 7 days. Endothelial blood-barrier integrity was assessed indirectly using spinal cord water content. Results : Zymography and Western blot analysis demonstrated rapid up-regulation of MMP-9 protein levels in spinal cord after ischemic onset. Expressions and activities of MMP-9 showed a significant increased at 6 h after the photothrombotic ischemic event, and reached a maximum level at 24 h after the insult. By contrast, activated MMP-2 was not detected at any time point in either the experimental or the control groups. When compared with the control group, a significant increase in spinal cord water content was detected in rats at 24 h after photothrombotic SCI. Conclusion : Early up-regulation of MMP-9 might be correlated with increased water content in the spinal cord at 24 h after SCI in rats. Results of this study suggest that MMP-9 is the key factor involved in disruption of the endothelial blood-barrier of the spinal cord and subsequent secondary damage after photothrombotic SCI in rats.

• 대한치과의사협회지
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• 제40권7호통권398호
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• pp.507-511
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• 2002

• Clinical and Experimental Pediatrics
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• 제48권2호
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• pp.197-203
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• 2005

목 적 : MMP 활동의 변화는 류마치스 관절염과 암 전위를 비롯한 여러 질환에서 보고되고 있다. 최근에 확장성 심근증에서 MMP 활동의 증가가 발표되었다. 아드리아마이신으로 유도된 심근증에서 MMP에 대한 보고는 없는 실정이다. 아드리아마이신으로 유도된 심근증에서 MMP, TIMP 유전자 발현을 연구하고 cytokine과의 관련성을 알아보고자 본 연구를 실시하였다. 방 법 : Sprague Dawley 쥐에 아드리아마이신 5 mg/kg을 1주일에 2번씩 2주간(누적 용량 : 20 mg/kg) 복강내 주사하였고, 정상쥐를 대조군으로 하였다. 2주 후에 쥐를 희생시켜서 혈청과 심장조직을 얻었다. 혈청에서 ELISA 원리로 MMP-2, TIMP-3, IL-6, TNF-${\alpha}$를 측정하였다. 심장에서 total RNA를 추출하였고, MMP-2, TIMP-3 IL-6, TNF-${\alpha}$ primer를 이용하여 PCR로 증폭하였다. 증폭된 DNA는 1% agarose gel에서 전기 영동하였고 UV light 아래에서 필름으로 촬영하였다. 결 과 : 혈청 MMP-2와 TIMP-3는 두 군 간에 유의한 차이가 없었다. 아드리아마이신군에서 IL-6은 $36.8{\pm}2.8pg/mL$, TNF-${\alpha}$은 $2.2{\pm}2.7pg/mL$로 정상군에 비해 유의한 증가를 보였다. 혈청 MMP-2와 TNF-${\alpha}$와는 r=0.41로 유의한 상관관계가 있었다. 심근 조직에서 MMP-2, IL-6, TNF-${\alpha}$는 발현되지 않았고, TIMP-3는 아드리아마이신군에서 대조군에 비해 유전자 발현이 감소되었다. 결 론 : 아드리아마이신으로 유도된 급성 심근증 모델에서는 심근에서 MMP, IL-6, TNF-${\alpha}$가 발현되지 않았고, TIMP 발현이 감소함을 알 수 있었다. 혈청 MMP와 TNF-${\alpha}$와의 상관성이 유의하게 높았으므로 TNF-${\alpha}$가 MMP 발현을 조절함을 시사해 준다. 앞으로 만성 심근증 모델에서 MMP, TIMP 발현에 대하여 연구할 예정이다.

• BMB Reports
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• 제53권4호
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• pp.212-217
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• 2020

Activation of peroxisome proliferator-activated receptor γ (PPARγ) serves as a key factor in the proliferation and invasion of breast cancer cells and is a potential therapeutic target for breast cancer. However, the mechanisms underlying this effect remain largely unknown. Heme oxygenase-1 (HO-1) is induced and over-expressed in various cancers and is associated with features of tumor aggressiveness. Recent studies have shown that HO-1 is a major downstream target of PPARγ. In this study, we investigated the effects of induction of HO-1 by PPARγ on TPA-induced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-κB /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ₂, a natural PPARγ ligand. 15d-PGJ₂ induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ₂. These results suggest that 15d-PGJ₂ inhibits TPA-induced MMP-9 expression and invasion of MCF-7 cells by means of a heme oxygenase-1-dependent mechanism. Therefore, PPARγ/HO-1 signaling-pathway inhibition may be beneficial for prevention and treatment of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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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).