• Advances in Traditional Medicine
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• v.5 no.4
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• pp.283-293
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• 2005

Our previous study showed that a novel synthetic shikonin derivative, 6-(1-hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) induced apoptosis. In the present study, we investigated its anti-metastatic activities as compared with shikonin because DMNQ S-52 was synthesized for overcoming weak points of shikonin such as high toxicity, low solubility and deleterious effects. DMNQ S-52 showed the weaker cytotoxicity $(IC_{50};\;12.3{\pm}1.6\;{\mu}M)$ against Lewis lung carcinoma (LLC) cells than that of shikonin $(IC_{50};\;4.2{\pm}1.1\;{\mu}M)$. DMNQ S-52, at non-toxic concentrations $(less\;than\;10\;{\mu}M)$, significantly inhibited the invasion and migration of LLC cells. DMNQ S-52 also significantly inhibited the production of MMP-9, MTl-MMP and uPAR. Moreover, daily i.p. administration of DMNQ S-52 at dose of 5 mg/kg in mice resulted in a potent inhibition of the primary tumor size of LLC in the lung as well as the metastasis of lymph nodes. These findings suggest that the DMNQ S-52 has therapeutic potential to inhibit metastasis via inhibition of MMP family and uPA/plasminogen system.

• CELLMED
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• v.8 no.3
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• pp.13.1-13.8
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• 2018

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone formation. The purpose of this study was to examine the effects of NNMBS 246 osteoblastic differentiation with associated signaling pathways. NNMBS 246 markedly increased alkaline phosphatase (ALP) activity and calcium nodule formation. Stimulation with NNMBS 246 not only increased the differentiation markers (ALP, OPN, OCN) level and transcription markers (RUNX2, Osterix) mRNA expression but also upregulated the ECM molecules and OPG mRNA expression. Treatments of NNMBS 246 downregulated MMPs (MMP-1, MMP-2, MMP-9), but RANKL mRNA expression. Furthermore, NNMBS 246 activated osteoblastic differentiation markers and formed calcium nodules in human periodontal ligament cells (hPDLCs) and cementoblast cells. NNMBS 246 induced phosphorylation of MAPKs, Akt, nuclear p65 and IkB-${\alpha}$. BMP-2/Smad and ${\beta}$-catenin signaling pathways were activated by NNMBS 246. Sirtinol (SIRT1 inhibitor) inhibited NNMBS 246-induced osteoblastic differentiation markers mRNA expression. These results suggested that NNMBS 246 has the potential to enhance osteoblastogenesis probably through the activation of BMP/Smad and ${\beta}$-catenin signal pathways, and SIRT1 plays as critical mediator in bone anabolic effect of NNMBS 246.

• Journal of Nutrition and Health
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• v.38 no.2
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• pp.104-111
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• 2005

Tumor invasion is composed of four steps: cell adhesion to the extracellular matrix, degradation of the extracellular matrix components, tumor cell motility followed by cell detachment. Matrix metalloproteinases (MMPs) are important proteinases that associated with degradation of matrix component. Epigallocatechin gallate (EGCG) is a major polyphenotic constituent of green tea. In the study, we examined the anti-invasive and MMP activity suppression effects of EGCG in MDA-MB-231 human breast cancer cells. MDA-MB-23l human breast cancer cells were cultured with various concentrations 0 - 100 μM of EGCG. EGCG significantly inhibited the cell adhesion to the fibronectin. Cell motility through gelatin filter and invasion to Matrigel were inhibited dose-dependently by EGCG treatment. EGCG also inhibited the activities of MMP-2, -9 and the amount of MMP-9 (α = 0.05). Therefore, EGCG may contribute to the potential beneficial food component to prevent the invasion and metastasis in breast cancer. (Korean J Nutrition 38(2): 104～111, 2005)

• BMB Reports
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• v.42 no.7
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• pp.427-432
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• 2009

Orthodontic tooth movement results from the combinational process of both bone resorption and formation in the compressive and tension sides, respectively. However, the genes responsible for new bone formation in tension sides have not been determined. In this study, we used DNA microarray and real-time RT-PCR to identify genes in human periodontal ligament (PDL) cells that undergo significant changes in expression in response to static tensional forces (2 or 12 hours). The genes found were alkaline phospatase (ALP), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and several collagen genes. Furthermore, an ELISA evaluating the expression of VEGF, type IV collagen and MMP-2 found levels significantly increased after 24 and 72 hours (P < 0.05). ALP activity was also increased after 24 hours (P < 0.05). Collectively, we found the genes up-regulated in our study by the static tensional force are related to osteogenic processes such as matrix synthesis and angiogenesis.

• Journal of Ginseng Research
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• v.35 no.3
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• pp.315-324
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• 2011

This study investigated the effect of red ginseng extract on metastasis of colon cancer cells in vitro and in vivo. Wound healing migration, cell motility, invasion, and activity, protein expression, and mRNA expression of matrix metalloproteinases (MMPs) were examined in SW480 human colon cancer cells. SW480 cells were cultured with or without $100{\mu}g/L$ PMA in the absence or presence of various concentrations (100, 200, or $300{\mu}g/mL$) of red ginseng extract. Red ginseng extract treatment caused signifi cant suppression of cell motility and invasion (p<0.05) in SW480 cells. Red ginseng extract inhibited MMP-2 and MMP-9 activity and their protein and mRNA expression in a dose-dependent manner (p<0.05) in SW480 cells. For experimental metastasis, BALB/c mice were injected intravenously with CT-26 mouse colon cancer cells in the tail vein, and were orally administered various concentrations (0, 75, 150, or 300 mg/kg body weight) of red ginseng extract for 3 weeks. Numbers of pulmonary nodules were signifi cantly decreased in mice that were fed red ginseng extract (p<0.05). Plasma MMP-2 and MMP-9 activity signifi cantly decreased in response to treatment with red ginseng extract in mice (p<0.05). These data suggest that red ginseng extract may be useful for prevention of cancer invasion and metastasis through inhibition of MMP-2 and MMP-9 pathways.

• Journal of Chest Surgery
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• v.44 no.6
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• pp.387-391
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• 2011

Background: The relationship between the degree of expression of matrix metalloproteinases or tissue inhibitor of metalloproteinases and venous reflux remains to be investigated. Materials and Methods: Primary varicose vein tissues were obtained from 23 patients, 18 females and 5 males, aged from 19 to 73. Cephalic or basilic veins were obtained for the control group from 10 patients who underwent vascular access for maintenance hemodialysis. Two operative techniques (high ligation with stripping or endovenous laser coagulation) were used. The expression of matrix metalloproteinase-2 and 13 and tissue inhibitor of metalloproteinase-4 in the varicose vein group and control group was assessed semi-quantitatively by immunohistochemical slides stained with primary antibodies. Results: Twenty (87%) of the varicose vein group patients had greater or lesser saphenous vein diseases with reflux. The focal weak (+) stain for matrix metalloproteinases-2, and 13, and tissue inhibitor of matrix metalloproteinase-4 was dominant in the varicose vein group; the focal or diffuse strong stain (++ or +++) was prevalent in the control group. The differences were statistically significant (p<0.01). The degree of reflux and the duration of symptoms were not significantly related to the expression of MMP-13 (p=0.317 and p=0.654, respectively). Conclusion: Further study should be performed to investigate the relationship between the clinical characteristics related to venous hypertension or reflux and expression of MMPs and TIMP in varicose veins.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1105-1110
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• 2014

Objective: Metastases and invasion are the main reasons for oncotherapy failure. Momordica cochinchinensis (Mu Bie Zi in Chinese) had been used for a variety of purposes, and shown anti-cancer action. In this article, we focused on effects on regulation of breast cancer cell ZR-75-30 metastases and invasion by extracts of Momordica cochinchinensis seeds (ESMCs). Methods: Effect of ESMCs on ZR-75-30 human breast cancer cells proliferation were evaluated by MTT assay and on invasion and migration by wound-healing and matrigel invasion chamber assays. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: ESMC revealed strong growth inhibitory effects on ZR-75-30 cells, and effectively inhibited ZR-75-30 cell invasion in a dose-dependent manner. Western blot and gelatin zymography analysis showed that ESMC significantly inhibited the expression and secretion of MMP-2 and MMP-9 in ZR-75-30 cells. Conclusions: ESMC has the potential to suppress the migration and invasion of ZR-75-30 cancer cells, and it might prove to of interest in the development of novel inhibitors for breast cancer.

• Nutrition Research and Practice
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• v.5 no.5
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• pp.375-380
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• 2011

This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 ${\mu}mol$/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 ${\mu}mol$/L within 48 h. Inorganic sulfur significantly decreased cell motility and invasion in the MDA-MB-231 cells in a dose-dependent manner (P<0.05), as determined using a Boyden chamber assay and a Matrigel chamber. The activities of MMP-2 and MMP-9 were significantly reduced by inorganic sulfur in a dose-dependent manner (P<0.05). The inorganic sulfur also significantly inhibited MMP-2 and MMP-9 expression in the cells (P<0.05). These data suggest that inorganic sulfur can suppress cancer cell motility and invasion by inhibiting MMP-2 and MMP-9 activity and gene expression in MDA-MB-231 cells.

• YAKHAK HOEJI
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• v.50 no.2
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• pp.99-104
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• 2006

Prostaglandins biosynthesis and nitric oxide production have been implicated in the process of inflammation. In this study we investigated on the effects of ethyl acetate extract of Angelica Koreana Radix (EAKR) on the activities of prostaglandin $E_2\;(PGE_2)$, proteoglycan (PG) degradation and nitric oxide synthase (NO) in inflammation cytokines-activated rabbit articular chondrocytes. EAKR exhibited inhibitory activities on NO production and $PGE_2$ production as $73.08\%\;and\;89.49\%$, respectively at $20{\mu}g/ml$ and inhibited the degradation of PG in a concentration-dependent manner Zelatin zymography analysis demonstrated that EAKR significantly inhibited MMP-2, 9 expression in chondrocytes. In vivo, EAKR was shown to have inhibitory effects on acetic acid-induced pain. This study suggests that modulation of $PGE_2$, NO, PG degradation and MMP-2, 9 by EARK may be important in the prevention of inflammation and osteroarthritis.

• BMB Reports
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• v.41 no.4
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• pp.322-327
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• 2008

In this study, we compared the gene expression profiles of non-syndromic hyperplastic dental follicle (HDF) fibroblasts and normal dental follicle (NDF) fibroblasts using cDNA micro-arrays, quantitative PCR, and immunohistochemical staining. Microarray analysis showed that several collagens genes were upregulated in the HDF's, including collagen types I, IV, VIII, and XI and TIMP-1, -3, and -4 (fold ratio > 2.0). In contrast, the expression of MMP-1, -3, -10, and -16 together with IL-8 was more than two fold downregulated. The differential expression of the genes encoding alkaline phosphatase, MMP-1, -3, -8, and IL-8 was confirmed by quantitative RT-PCR, while that of 24 HDFs and 18 NDFs was confirmed by immunohistochemical analysis. However, HDFs showed stronger expression of MMP-3 than NDFs (P < 0.001). Collectively, these results indicate that defective regulation of MMPs mediating connective tissue remodeling may be responsible for abnormal tooth eruption.