• BMB Reports
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• v.40 no.6
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• pp.1069-1076
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• 2007

Cancer cells, characterized by local invasion and distant metastasis, are very much dependant on the extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we reported the effects of disulfiram, a clinically used anti-alcoholism drug, on tumor invasion suppression, as well as its effects on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram has been used for alcohol aversion therapy. However, recent reports have shown that disulfiram may have potential in the treatment of human cancers. Herewith, we showed that the anti-tumor effects of disulfiram, in an invasion assay using U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that inhibits expression of genes and proteins responsible for both cell and non-cell mediated invasion on pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These observations raise the possibility of disulfiram being used clinical for the inhibition of cancer invasion.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.2
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• pp.105-110
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• 2017

Prolonged exposure to solar ultraviolet A (UVA) radiation has been known to cause premature skin aging (photo-aging). UVA radiation generates ROS thereby induce degenerative changes of skin such as degradation of dermal collagen, elastic fibers. Matrix metalloproteinases (MMPs), the proteolytic enzymes have been implicated as a major player in the development of UVA-induced photo-aging. Many studies have been conducted to block the harmful effects of UV radiation on the skin. Recently, we are interested in the availability of fermented red ginseng (FRG) as natural matrix metalloproteinases inhibitors (MMPIs). The efficacy difference between red ginseng and FRG has been compared. Both RG and FRG have no cytotoxic effects below the concentration of $300{\mu}g/ml$. Human dermal fibroblasts (HDFs) were pretreated with FRG or RG for 24h, followed by irradiation of UVA. Then, we measured the intracellular ROS production and the expression of MMP, $IL-1{\beta}$ at the mRNA level. We also examined the intracellular localization of $NF-{\kappa}B$ and MMP-9 on the FRG or RG treated and UVA-irradiated HDFs. FRG decreased the intracellular ROS production elicited by UVA. In addition, FRG decreased the mRNA expression of MMP-3, MMP-9, and $IL-1{\beta}$ more efficiently than RG. Furthermore, FRG suppressed the nuclear localization of $NF-{\kappa}B$, and the expression of MMP-9. Taken together, our results suggest that FRG is promising agents to prevent UVA-induced photo-aging by suppressing MMP expression and inflammation.

• The Korea Journal of Herbology
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• v.32 no.1
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• pp.83-89
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• 2017

Objectives : The present study was designed to determine the effects of mixture of Achyranthis Japonicae Radix, Scutellariae Radix, and Acanthopanacis Cortex on monosodium iodoacetate (MIA)-induced osteoarthritis in rats. The mixture was composed of Achyranthis Japonicae Radix, Scutellariae Radix, and Acanthopanacis Cortex extracts. Methods : Arthritis was induced by injection of MIA into knee joints of rats. At the end of experiment, gross examination on the articular structures of knee joints were performed. Proteoglycan (PG) contents in articular cartilages were analysed as well. Tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) and $interleukin-1{\beta}$ ($IL-1{\beta}$) contents in synovial fluids were measured by ELISA method and matrix metalloproteinase 2 (MMP2), MMP9, and tissue inhibitors of metalloproteinase 1 (TIMP1) mRNA were measured by a realtime PCR. Results : The surfaces of the articular cartilage were observed. The severity of osteoarthritis in the treated group were alleviated compared with control group. PG contents in articular cartilages of the treated group were increased compared with control group. $IL-1{\beta}$ contents in synovial fluids of the treated group were significantly decreased compared with control group. MMP2 and MMP9 mRNA contents in articular cartilages were significantly decreased compared with control group and TIMP1 mRNA contents were increased compared with control group. Conclusions : On the basis of these results, we concluded that Achyranthis Japonicae Radix-containing mixture treatment has anti-arthritic effects on the MIA-induced osteoarthritis in rats. And the effects were related with the reduction of $IL-1{\beta}$ in synovial membranes and the consequent reduction of MMP2 and MMP9 expressions.

• Journal of dental hygiene science
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• v.22 no.2
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• pp.99-107
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• 2022

Background: Obesity weakens acquired immunity and causes infection. This study aimed to investigate the relationship between the inflammatory markers in the gingival crevicular fluid and serum and periodontal bacteria in saliva through obesity control for 4 weeks. Methods: Forty-six subjects with a body mass index (BMI) of ≥23 kg/m² stayed in the camp for 4 weeks, followed by exercise and a low salt-low fat diet. Body size measurements, oral examinations, blood, saliva, and gingival crevicular fluid were collected before and after the program. C-reactive protein (CRP) in serum, matrix metalloproteinase (MMP)-8, MMP-9, and interleukin (IL)-1β in the gingival sulcus fluid were measured. After extracting bacterial genomic DNA from saliva, the presence of periodontal bacteria were detected using Taq probe. The relationship of each index before and after the program was analyzed through paired t-test and partial correlation analysis. Results: Campylobacter rectus (Cr) increased after the program, and there was no significant change in other bacteria. Serum CRP and Fusobacterium nucleatum (Fn), Aggregatibacter actinomycetemcomitans, Cr, ratio of Fn, and ratio of Cr had a positive relationship at baseline; however, the relationship was not significant after the program. Ratio of Prevotella intermedia had a positive relationship with MMP-9, MMP-8, IL-1β at baseline. Moreover, the ratio of Treponema denticola and the ratio of Tannerella forsythia showed a positive relationship with MMP-8, MMP-9, and IL-1β. The relationship between the ratio of Porphyromonas gingivalis and IL-1β showed a constant positive relationship at baseline and after the program. Conclusion: Obesity control program in subjects with a BMI of ≥23 kg/m² accompanied by diet and exercise did not affect the changes in periodontal bacteria itself, but changes in the relationship between periodontal bacteria and serum CRP, the relationship between the inflammatory index in the gingival crevicular fluid and periodontal bacteria was observed.

• Journal of Periodontal and Implant Science
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• v.34 no.1
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• pp.139-148
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• 2004

MMPs(Matrix metalloproteinases)는 치주질환에서 주된 조직파괴단백분해효소인 것은 알려져 있고 TIMPs(Tissue inhibitor of Matrix metalloproteinase)는 MMPs의 작용을 억제한다라고 알려져 있다. 이 둘간의 불균형으로 인해서 조직파괴가 더 가속화될 수 있다. 이 두 연구의 목적은 ELISA kit를 사용하여 특정 MMPs(1,2,3,8,9,13)과 TIMPs(1,2)의 양이 건강한 환자와 비교하여서 치주염 환자에서 달라지는지 알아보고 MMPs(1,2,3,8,9,13), TIMPs(1,2)와 치은열구깊이와 GI score와의 관계를 알아보기로 한다. 8명의 만성 치주염 환자와 4명의 급속진행형 치주염 환자가 실험군으로 참여하였고 5명의 건강한 치주조직을 환자가 대조군으로 참여하였다. 임상적인 측정은 GI score와 치주낭측정을 통하여 이루어졌다. 8명의 만성 치주염을 가진 환자와 4명의 급속진행형 치주염을 가진 환자에서 각각 치주낭 깊이가 3mm이하인 부위에서 6개의 치은열구액 표본과 치주낭 깊이가 6mm 이상인 곳에서 6개의 치은열구액 표본을 채취하였다. 건강한 치주조직을 가진 5명의 환자는 단지 치주낭깊이가 3mm 이하인 건강한 부위에서만 치은열구액 표본을 제공하였다. MMPs(1,2,3,8,9,13)과 MIMPs(1,2)의 측정은 Human Biotrack ELISA kit를 사용하여서 측정하였다. 통계처리는 MMPs, MIMPs의 실험군과 대조군의 차이는 Kruskal-Wallis test를 사용하였고 MMPs, TIMPs와 치주낭 깊이와 GI score의 관계정도는 Pearson's correlation coefficient를 사용하였다. 실험결과 대조군과 비교하여 만성 치주염 환자에서 치주낭 깊이가 6mm 이상인 부위에서 MMP9의 수치가 통계적으로 유의할만하게 높았으며(p=0.04) MIMP2의 수치가 대조군과 비교하여 치주낭 깊이가 3mm 이하인 부위를 가진 만성치주염 환자에서 통계적으로 유의할만하게 높았다(=0.049). MMPs(1,2,3,8,9,13), MIMPs(1,2)의 활동성과 치주낭 깊이의 관계에서 둘간의 통계적으로 유의할만한 관계는 존재하지 않았으나 MMP1(r=0.35)과 MMP2(r=0.31)가 상대적으로 높은 관계를 보였다. 또한 MMPs(1,2,3,8,9,13), MIMPs(1,2)의 활동성과 GI score의 관계에서도 둘간의 통계학적으로 유의할만한 관계는 존재하지 않으나 MMP1(r=0.4), MMP2(r=0.29), MMP9(r=0.26)가 상대적으로 높은 관계를 보였다. 이 실험의 결과로 볼 때 MMP9가 만성치주염 환자의 질환이 있는 부위에서만 염증의 지표가 될 수 있으며 MIMP2가 만성치주염 환자의 염증이 없는 부위에서 높은 농도로 존재하는 것으로 보아서 MIMP2가 MMPs에 대한 억제작용을 하여서 염증의 진행을 방해하는 역할을 한다라고 볼 수 있다.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3259-3264
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• 2012

Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and $40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.536-542
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• 2022

Background: In aged skin, reactive oxygen species (ROS) induces degradation of the extracellular matrix (ECM), leading to visible aging signs. Collagens in the ECM are cleaved by matrix metalloproteinases (MMPs). Syringaresinol (SYR), isolated from Panax ginseng berry, has various physiological activities, including anti-inflammatory action. However, the anti-aging effects of SYR via antioxidant and autophagy regulation have not been elucidated. Methods: The preventive effect of SYR on skin aging was investigated in human HaCaT keratinocytes in the presence of H₂O₂, and the keratinocyte cells were treated with SYR (0-200 ㎍/mL). mRNA and protein levels of MMP-2 and -9 were determined by real-time PCR and Western blotting, respectively. Radical scavenging activity was researched by 2,2 diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. LC3B level was assessed by Western blotting and confocal microscopy. Results: SYR significantly reduced gene expression and protein levels of MMP-9 and -2 in both H₂O₂-treated and untreated HaCaT cells. SYR did not show cytotoxicity to HaCaT cells. SYR exhibited DPPH and ABTS radical scavenging activities with an EC₅₀ value of 10.77 and 10.35 ㎍/mL, respectively. SYR elevated total levels of endogenous and exogenous LC3B in H₂O₂-stimulated HaCaT cells. 3-Methyladenine (3-MA), an autophagy inhibitor, counteracted the inhibitory effect of SYR on MMP-2 expression. Conclusion: SYR showed antioxidant activity and up-regulated autophagy activity in H₂O₂-stimulated HaCaT cells, lowering the expression of MMP-2 and MMP-9 associated with skin aging. Our results suggest that SYR has potential value as a cosmetic additive for prevention of skin aging.

• Biomedical Science Letters
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• v.19 no.1
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• pp.9-16
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• 2013

Elevated blood triglyceride (TG) levels correlate with development of atherosclerosis suggesting that TG may promote the development of this disease. During atherosclerosis, TG is taken up by tissue macrophages which result in dramatic changes in various secreted factors. One such factor is the family of matrix metalloproteases (MMP) which are involved in tissue remodeling during both physiological and pathological processes. In this study, we examined the MMP expression profile in PMA-differentiated THP-1 macrophages treated with TG. We found that TG-treated THP-1 macrophages showed decreased expression of MMP-3, MMP-7, MMP-8 and MMP-9 in a time- and dose-dependent manner. In contrast, expression of MMP-1, MMP-2, and MMP-10 remained relatively unchanged after TG treatment. In addition, we found that expression of select MMPs was affected by various inhibitors of signaling pathways. In particular, expression of MMP-3 was slightly recovered by cRAF and PLC signaling pathway inhibitors. These data suggests a possible role of MMPs in macrophages during TG-induced atherosclerosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5397-5402
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• 2013

The rates of morbidity and mortality of hepatocellular carcinoma (HCC) have not lessened because of difficulty in treating tumor metastasis. Mongolian Saussurea involucrata (SIE) possesses various anticancer activities, including apoptosis and cell cycle arrest. However, detailed effects and molecular mechanisms of SIE on metastasis are unclear. Thus, the present study was undertaken to investigate antimetastatic effects on HCC cells as well as possible mechanisms. Effects of SIE on the growth, adhesion, migration, aggregation and invasion of the SK-Hep1 human HCC cell line were investigated. SIE inhibited cell growth of metastatic cells in dose- and time-dependent manners. Incubation of SK-Hep1 cells with $200-400{\mu}g/mL$ of SIE significantly inhibited cell adhesion to gelatin-coated substrate. In the migration (wound healing) and aggregation assays, SIE treated cells showed lower levels than untreated cells. Invasion assays revealed that SIE treatment inhibited cell invasion capacity of HCC cells substantially. Quantitative real time PCR showed inhibitory effects of SIE on MMP-2/-9 and MT1-MMP mRNA levels, and stimulatory effects on TIMP-1, an inhibitor of MMPs. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by SIE, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 expression of SK-Hep1 cells. From these results, it was suggested that SIE could be used as potential anti-tumor agent.

• Korean Journal of Plant Resources
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• v.21 no.1
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• pp.96-102
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• 2008

Nelumbo nucifera Gaertn.(family Nymphaeaceae) has been used for summer heat syndrome as home remedy in Japan, China and Korea. Although whole plant parts are edible, root is commonly consumed. It has been reported that rhizome extract showed anti-diabetic and anti-inflammatory effects. However, in spite of usefulness for treatment of various diseases, the effect of Nelumbo nucifera rhizome(NNR) on proliferation, migration and matrix degrading enzymes-matrix metalloproteinsases(MMPs), the expression of which degrades extracellular matrix(ECM) leading to metastasis, has not been fully elucidated. We examined the effect of hot water extract of NNR on the proliferation, migration and secretion of MMP-2 and MMP-9 in rat smooth muscle cells(rSMC), epidermoid cancer cells(A431) and breast cancer cells(MDA-MB-231). The proliferation assay was carried out using MTT assay, the principle of which depends upon the conversion of MTT by mitochondrial dehydrogensases of viable cells to formazan crystals. The effect of NNR on migration of cells was examined using wound healing assay. Our results showed that there was inhibition in the proliferation, migration and expression of MMP-2 and MMP-9 in dose dependent fashion in all the cells used. Thus, we concluded that NNR could be used as traditional medicine in the treatment of various diseases where proliferation, migration and MMPs' expression plays a pathological role like in restenosis and metastasis.