• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.422-429
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• 2009

Invasion and metastasis is the main cause of cancer mortality. Angiogenesis is a prerequisite for the tumor growth and metastasis. Matrix metalloproteinases (MMPs) are the key enzymes playing in the invasive growth and metastasis of cancer as well as angiogenesis. Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L), has been reported to suppress cancer invasion and angiogenesis. In the present study, we investigated the antiinvasive effects of xanthohumol (1) and its synthetic derivatives, 4'-O-methylxanthohumol SEM ether (2), xanthohumol C (3), and xanthohumol C MOM ether (4) in relation to MMP expression in HT-1080 human fibrosarcoma cells. The compound 1 and its derivative, 3 and 4, significantly inhibited serum-induced HT-1080 cell invasion, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced activity and expression level of MMP-2 and MMP-9 in a concentration-dependant manner. In addition, they inhibited TPA-enhanced expression of MT1-MMP with relatively weak inhibition in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 level. The compound 1 significantly decreased the cell viability, whereas the derivatives, 2 and 3 showed no cytotoxicity, and compound 4 showed slight cytotoxicity in the cells. Furthermore, in a chick chorioallantoic membrane (CAM) assay, the derivatives 3 and 4 dose-dependently suppressed vascular endothelial growth factor (VEGF)-induced angiogenesis, which is similar to that of compound 1. Taken together, the results indicate that compounds 3 and 4 may be valuable anti-angiogenic agents in the treatment of chronic diseases such as cancer and inflammation working through suppression of MMP-2 and MMP-9.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.183-188
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• 2013

Ultraviolet (UV) B irradiation induces the production of matrix metalloproteinases (MMPs), which are responsible for the degradation or synthesis inhibition of collagenous extracellular matrix in connective tissues, causing skin photoaging. In this study, we examined the inhibitory effect of MMP-1 expression of yam extract in tumor necrosis factor-alpha (TNF-${\alpha}$)-stimulated human dermal fibroblast neonatal (HDFn) cell and preventive effect of UVB-induced damage in hairless mice skin. The synthesis of procollagen and the release of MMP-1 in HDFn cells were measured by EIA kit and MMP-1 assay kit, respectively. UVB radiation was applied to the backs of the mice three times a week for 8 weeks. Mice were randomly divided into three groups, and were topical application with the Dioscorea batatas (DB, 6%) or vehicle. Reduction of TNF-${\alpha}$-induced procollagen synthesis was increased by DB (50 ug/ml), which was higher than positive control group (TGF-${\beta}$). Also, pre-treatment of HDFn cells with DB inhibited TNF-${\alpha}$-induced release of MMP-1. In vivo study, we found that preventive effect of DB against UV-induced epidermal thickness. DB suppressed the expression of MMP-3 and MMP-13 induced by UVB irradiation. Our results show that DB have preventive effect of UV-induced skin damage in hairless mice.

• BMB Reports
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• v.46 no.11
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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.

• Korean Journal of Head & Neck Oncology
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• v.21 no.2
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• pp.121-125
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• 2005

Objectives: To investigate the role of MMP-2 and TIMP-2 in the invasion and metastasis of thyroid papillary microcarcinomas. Materials and Methods: We performed immunohistochemical study on MMP-2 and its tissue inhibitor (TIMP-2) using tissue microarrays containing 2 cores of 40 microPTC and 8 non-neoplastic thyroid tissue. The expression intensity was semiquantitatively scored as -, ${\pm}$, +1, +2, and +3. Results: Both MMP-2 and TIMP-2 expression was observed in all tumors(100%) and in 1 of 8 non-neoplastic tissue(12.5%), and the positive staining was restricted to the epithelial cells. In 17 and 23 tumors with or without extrathyroid invasion, respectively, 8(47%) and 10(43%) cases showed moderate to strong(+23) positivity for MMP-2. TIMP-2 expression was moderate to strong in 13 cases(76%) and 16 cases(70%) in each group. In multifocal and solitary tumors, 3 of 6(50%) and 11 of 21(52%) cases showed moderate to strong MMP-2 expression, and 5/6(83%) and 15/21(71%) showed moderate to strong TIMP-2 expression. Conclusion: There is no relationship between MMP-2 or TIMP-2 expression and extrathyroid invasion or tumor multifocality in papillary microcarcinoma of the thyroid gland.

• Journal of Life Science
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• v.18 no.4
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• pp.503-508
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• 2008

Deep sea water from the East sea was tested for breast cancer chemoprevention and metastasis by measuring the activities of cytochrome P450 1A1 and aromatase, invasiveness, and activity and expression of matrix metalloproteinase (MMP)-9 in breast MDA-MB-231 cancer cell. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P450 1A1 activity. Deep sea water showed 27.1, 45.4 and 51.9% inhibition of microsomal aromatase activity at the hardness of 600, 800 and 1,000, respectively. In addition deep sea water inhibited not only the invasiveness of 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MDA-MB-231 cells through matrigel-coated membrane in a hardness-dependent manner but also the activity and expression of MMP-9 in MDA-MB-231 cell.

• Korean Journal of Plant Resources
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• v.32 no.3
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• pp.207-219
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• 2019

Ultraviolet (UV) radiation is associated with the development of extrinsic skin aging. We performed in vivo assays in order to investigate the protective effect of a combination of grapefruit and rosemary extracts (cG&Re) on UVB-induced skin aging. The results indicated that cG&Re displayed elastase inhibitory activity in a dose-dependent manner. Topical application of cG&Re mitigated photo-aging related lesions such as skin erythema and thickening in photo-aged BALB/c mice dorsal skin, by preventing UVB-induced collagen degradation. Immunohistochemical analyses revealed that cG&Re stimulated SIRT-1 expression, and suppressed MMP-1 and $IL-1{\beta}$ expression. It was observed that expression of MMP-1 and -13 mRNA was downregulated in the cG&Re-treated group. Furthermore, cG&Re treatment drastically suppressed protein expression of MMP-1 and regulated the phosphorylation of p-38 kinase. As expected, oral administration of cG&Re resulted in the same SIRT-1, MMP-1, and $IL-1{\beta}$ expression patterns observed upon topical application of cG&Re in the UV-induced mice model. Overall, the current results demonstrated that cG&Re attenuated both the downregulation of MMP-1 expression and up-regulation of SIRT-1 expression, as well as decreased phosphorylation of MAPK in UVB-induced skin ageing mice model, suggesting that cG&Re might be used as an internal food ingredient for beauty-purposes as well as a functional food material.

• Journal of the Korean Chemical Society
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• v.67 no.2
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• pp.129-136
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• 2023

Osteoarthritis is to the abnormality of the inflammatory response of joint tissue caused by various causes such as aging, and muscle loss. In this study, the activity in joint inflammation was verified using SKBE, a plant extract, and the expression levels of arthritis-inducing proteins including MMP-1, MMP-3, MMP-13, and collagen type II in vitro were compared and analyzed. Furthermore, we synthesized α-spinasterol, an active ingredient of SKBE, by the previously reported synthesis method and these findings could provide a new starting point for the development of treatments for osteoarthritis.

• Journal of Life Science
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• v.32 no.8
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• pp.622-632
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• 2022

The purpose of this study was to investigate activities as functional cosmetic materials, focusing on Rhododendron brachycarpum (RB) and Rhododendron fortunei (RF). The tyrosinase inhibitory effect, related to skin-whitening, was 32.6% and 39.3% respectively at the concentration of 1,000 ㎍/ml. The elastase inhibitory effect, related to skin anti-wrinkling activity, was 30% and 36.2% at 1,000 ㎍/ml concentration. Collagenase inhibitory activity showed 77.7%, and 80.2% respectively at 1,000 ㎍/ml concentration, which demonstrated excellent inhibitory activity. For a cell viability test, that measured on fibroblast cells by RB and RF extracts. Furthermore, the cell viability test showed 100.9% and 98.9% with cell viability at 100 ㎍/ml concentration in CCD-986Sk. The protein expression inhibitory effect of RB and RF extracts was measured by western blot at 25, 50, and 100 ㎍/ml concentrations, and the β-actin was used as a positive control. As a result, western blot of RB and RF extracts was measured by the expression inhibition rate of the MMP-1, MMP-2, MMP-3 protein, and was decreased by 67.2%, 65.5%, 13.6%, and 89.1%, 85.0%, and 62.7% at 100 ㎍/ml concentration. The mRNA expression inhibitory effect of RB and RF extracts was measured by RT-PCR at 25, 50, and 100 ㎍/ml concentrations, and the GAPDH was used as a positive control. According to the results of RT-PCR of RB and RF extracts, the expression inhibition rate of the MMP-1, MMP-2, and MMP-3 mRNA was decreased by 70.1%, 9.1%, 37.9%, and 38.2%, 8.3%, 57.3% at 100 ㎍/ml concentrations. So, RB and RF extracts showed the anti-wrinkle effectiveness as a functional cosmetic material.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.3
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• pp.1-13
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• 2009

Objectives : This study evaluates neuroprotective effect of Gastrodiae Rhizoma on apoptosis in the cerebral infarct. Methods : Cerebral infarct was induced by the middle cerebral artery occlusion (MCAO) for 2 hours with intraluminal thread method in Sprague-Dawley rats. Then ethanol extract of Gastrodiae Rhizoma was administered orally for 3 days. Infarct area and volume were evaluated with TTC staining. Neuronal apoptosis was identified with TUNEL labeling. Apoptosis modulatory effect was observed with immunohistochemical Bax, Bcl-2, iNOS, and MMP-9 expressions in penumbra. Results : 1. Ethanol extract of Gastrodiae Rhizoma reduced infarct size partly and volume significantly of in the MCAO rat brain. 2. Ethanol extract of Gastrodiae Rhizoma reduced TUNEL positive cell ratio in the penumbra of MCAO rat brain significantly. 3. Ethanol extract of Gastrodiae Rhizoma suppressed Bax, iNOS and MMP-9 expression in the penumbra of MCAO rat brain significantly. 4. Ethanol extract of Gastrodiae Rhizoma did not change Bcl-2 expression in the penumbra of MCAO rat brain. But expression ratio of Bcl-2 against Bax was increased in the Gastrodiae Rhizoma group. Conclusions : These results suggest that Gastrodiae Rhizoma plays an anti-apoptotic neuroprotective effect through suppression of Bax, iNOS, and MMP-9 expressions and relative up-regulation of Bcl-2 in the ischemic brain tissue.

• Animal cells and systems
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• v.13 no.2
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• pp.113-118
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• 2009

Extracts derived from various medical mushrooms have been reported to have antitumor and immuno-modulatory properties. In order to investigate the antitumor activity of keumsa Linteusan, the water extract of Phellinus Iimteus, HT1080 cells, a human fibrosarcoma cell line, were treated with it and changes in cellular migration potential was tested in vitro. At a concentration range below 1,000 $\mu$g/mL, Linteusan blocked, in a dose dependent manner, the migration of cells through Matrigel as well as Boyden chamber without affecting the viability of the cells. Prolonged treatment of HT1080 cells with Linteusan suppressed TNFa induced production of matrix metalloproteinase (MMP)-9 as well as basal level expression of MMP-2. Linteusan also affected the adhesion of the cells to fibronectin-coated surfaces. The effect of Linteusan on cell signaling pathways was also tested. Linteusan specifically affected TNF-$\alpha$ induced phosphorylation of AKT in a dose-dependent manner, while phosphorylation levels of ERK remained unaffected. These data indicate that Linteusan blocks the migration of HT1080 cells by affecting various processes associated with cell migration such as the expression of matrix degradingenzymes,cell adhesion, and AKT-medicated cellular signaling pathways.