• Journal of Oral Medicine and Pain
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• v.44 no.4
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• pp.160-168
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• 2019

Purpose: To search the salivary factors that objectively indicate an pain in myalgia patients with temporomandibular joint disorder (TMD) and determine the possibility of the factors as pain-biomarkers. Methods: Participants consisted of pain-free 15 persons (male 7, female 8, mean age±standard deviation (SD); 26.8±16.04 years) and 45 myalgia patients with TMD (male 21, female 24, mean age±SD; 27.98±13.01 years). They were divided into a pain-free group (numerical rating scale [NRS] score 0), a mild pain group (NRS 1-4), a moderate pain group (NRS 5-6), and a severe pain group (NRS 7-10) and members of all groups were age, sex matched. Interleukin-8 (IL-8) and matrix metalloprotease 9 (MMP-9) were selected as pain biomarkers, by searching the Gene Expression Omnibus database and analyzing pain-related genes. Enzyme-linked immunosorbent assays were used to measure the concentration of IL-8 and MMP-9 in the patients' saliva. Results: IL-8 and MMP-9 levels were statistically significantly higher in pain groups than in the pain-free group. Greater differences were observed in patients with acute pain (with painful duration under 3 months) than in the control group and in female patients than in male. Conclusions: Salivary IL-8 and MMP-9 may play a role as biomarkers of myalgia in patients with TMD.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.191-201
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• 2005

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4815-4822
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• 2012

Invasion and metastasis are the major causes of cancer-related death. Pharmacological or therapeutic interventions such as chemoprevention of the progression stages of neoplastic development could result in substantial reduction in the incidence of cancer mortality. (-)-Epigallocatechin-3-gallate (EGCG), a promising chemopreventive agent, has attracted extensive interest for cancer therapy utilizing its antioxidant, anti-proliferative and inhibitory effects on angiogenesis and tumor cell invasion. In this study, we assessed the influence of EGCG on the proliferative potential of HeLa cells by cell viability assay and authenticated the results by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Further we analyzed the anti-invasive properties of EGCG by wound migration assay and gene expression of MMP-9 and TIMP-1 in HeLa cells. Our results indicated that EGCG induced growth inhibition of HeLa cells in a dose- and time-dependent manner. It was observed that cell death mediated by EGCG was through apoptosis. Interestingly, EGCG effectively inhibited invasion and migration of HeLa cells and modulated the expression of related genes (MMP-9 and TIMP-1). These results indicate that EGCG may effectively suppress promotion and progression stages of cervical cancer development.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.1
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• pp.22-28
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• 2014

Flos Sophorae, the dried flower bud of Sophora japonica L, possesses anti-inflammatory properties, prevents and treats blood capillary and hypertension diseases and can also be used as a hemostat. However, the effect of Flos Sophorae on breast cancer invasion is unknown. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of Flos Sophorae extract (FSE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in Michigan Cancer Foundation-7 (MCF-7) cells. FSE inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-${\kappa}B$). These results indicate that FSE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-${\kappa}B$ pathway in MCF-7 cells. Thus, FSE may have therapeutic potential for controlling breast cancer invasiveness.

• The Journal of the Korean bone and joint tumor society
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• v.13 no.2
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• pp.88-95
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• 2007

Purpose: The purpose of this study was to compare the proapoptotic effects of matrix metal-loproteinase inhibitor (MMPI) and doxorubicin on wild-type p53 osteosarcoma cell line, socalled U2OS cell line. Materials and Methods: U2OS cells were treated with MMP inhibitor III (MMPI III) and doxorubicin, either respectively or simultaneously. In cells treated with doxorubicin, Fas-neutralizing antibody so called ZB4 was additionally treated to examine whether the doxorubicin played a role through the Fas/FasL pathway. Cells were analysed regarding to apoptosis and cell death by flow cytometry. Results: U2OS cells incubated with doxorubicin showed significant amount of cell death in dose-dependent manner. However, those incubated with MMPI III mostly remained viable state. In addition, there is no relationship between two drugs. Cells treated with doxorubicin and ZB4 at the same time did not show down regulation of apoptosis through inhibition of Fas/FasL pathway. Conclusion: It is important to re-examine MMP inhibitor's effect on other osteosarcoma cell line with wild-type p14 as well as wild-type p53 to evaluate its proapoptotic effect.

• BMB Reports
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• v.46 no.4
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• pp.201-206
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• 2013

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is an isothiocyanate found in some cruciferous vegetables, especially broccoli. Sulforaphane has been shown to display anti-cancer properties against various cancer cell lines. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in cancer cell invasion. In this study, we investigated the effect of sulforaphane on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. TPA-induced MMP-9 expression and cell invasion were decreased by sulforaphane treatment. TPA substantially increased NF-${\kappa}B$ and AP-1 DNA binding activity. Pre-treatment with sulforaphane inhibited TPA-stimulated NF-${\kappa}B$ binding activity, but not AP-1 binding activity. In addition, we found that sulforaphane suppressed NF-${\kappa}B$ activation, by inhibiting phosphorylation of $I{\kappa}B $ in TPA-treated MCF-7 cells. In this study, we demonstrated that the inhibition of TPA-induced MMP-9 expression and cell invasion by sulforaphane was mediated by the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.5
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• pp.562-571
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• 2017

In this study, we investigated the anti-oxidant activities [electron-donating ability (EDA), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging ability, and reactive oxygen species (ROS) inhibitory activity], anti-wrinkle activities [collagenase inhibitory activity, suppression and/or phosphorylation of matrix metalloproteinases (MMPs), and mitogen-activated protein (MAP) kinase activity], and mRNA expression levels using reverse transcription-polymerase chain reaction (RT-PCR) assay in ultraviolet (UV) B ray ($50mJ/cm^2$)-irradiated human keratinocyte HaCaT cells. Josaengheugchal, Sinneungheugchal (SE), Shintoheug rice, Heugjinju rice, and Heugseol (HE) among colored rice varieties were reported to have excellent antioxidant properties. In the EDA and ABTS radical scavenging assays, extracts of the five colored rice varieties had scavenging activities of 72% at concentrations higher $50{\mu}g/mL$. In the collagenase inhibition assay, ethanol extracts of the five colored rice varieties showed high inhibitory effects of about 60% at concentrations higher $25{\mu}g/mL$. In the ROS inhibition assay, ethanol extracts of HE and SE showed very excellent inhibition efficacies at all concentrations. We determined molecular biological mechanisms of MMPs (MMP-1, -3, -8, and -13) and mitogen-activated protein kinase (MAPK) with HE, and the results show that HE suppressed expression of MMPs and phosphorylation of MAPK and increased expression of pro-collagen type I in UVB-irradiated cells. It was also confirmed by RT-PCR that HE reduced expression of MMPs mRNA. Therefore, these results suggest that HE has anti-wrinkle and collagen production effects and may be used as a material in the development of functional food and cosmetic industries.

• Journal of Life Science
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• v.33 no.6
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• pp.498-505
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• 2023

Solanum tuberosum Linnaeus cv Hongyoung, which represents red potato, was developed in Korea. Hongyoung is known to have anti-oxidant, anti-inflammatory, anti-viral, and anti-tumor properties, but no research has been conducted on the growth inhibition and apoptosis effects of hongyoung in YD-10B oral cancer cells. In this study, the combined treatment of hongyoung ethanol extract (HEE) and cisplatin were examined to determine its ability to inhibit cancer cell growth, induce apoptosis, and inhibit matrix metalloproteinases (MMP)-2 and MMP-9 cancer metastasis. The cell viability was investigated using a 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H- tetrazolium monosodium salt (MTS) assay, and the ability to induce apoptosis was analyzed using an FACS analyzer. The mRNA expression and protein activity of MMP-2 and MMP-9 were measured via RT-PCR and zymography. The YD-10B oral cancer cells showed an increase in growth inhibition as the concentration of HEE increased. The combination of 200 µM cisplatin and 500 ㎍/ml HEE reduced the growth of the YD-10B oral cancer cells by more than 50% compared to cisplatin alone. When phorbol 12-myristate 13-acetate (PMA)-treated YD-10B oral cancer cells were co-treated with 200 µM cisplatin and 500 ㎍/ml HEE, both the mRNA expression and protein activity of the MMP-2 and MMP-9 decreased. In addition, the percentage of the sub-G1 phase, which indicates apoptosis ability, more than doubled when treated in combination with 200 µM cisplatin and 500 ㎍/ml HEE than when cisplatin alone was used. The results of this study therefore suggest the possibility of using a combination of HEE and cisplatin in the development of effective drugs to treat oral cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.6
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• pp.782-788
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• 2013

Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae), colloquially known "Gujulcho" in Korea, has been used in traditional medicine for the treatment of various diseases, including cough, common cold, bladder-related disorders, gastroenteric disorders, hypertension, and inflammatory diseases, such as pneumonia, bronchitis, pharyngitis, and rheumatoid arthritis (RA) However, the effect of Chrysanthemum zawadskii var. latilobum on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of Chrysanthemum zawadskii var. latilobum extract (CZE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. CZE were not cytotoxic up to 100 ${\mu}g/ml$ concentration in the MCF-7 cell line. CZE decreased MMP-9 expression. TPA substantially increased NF-${\kappa}B$ DNA binding activity. Pre-treatment with CZE inhibited TPA-stimulated NF-${\kappa}B$ binding activity and NF-${\kappa}B$ related protein expression. To identify invasion ability of MCF-7 cells decreased by CZE, we used martrigel invasion assay. As a result, it is significantly decreased cell invasion. These results indicate that CZE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. Chrysanthemum zawadskii var. latilobum may have potential value in restricting breast cancer metastasis.

• YAKHAK HOEJI
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• v.56 no.1
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• pp.9-13
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• 2012

We previously reported that the extract of Taraxacum platycarpum (AF-343) had several biological properties such as skin hydration and anti-inflammatory effects, thereby AF-343 be a promising anti-atopic dermatitis agent. However, few studies have been conducted to evaluate its effect on modulation of extracellular matrix proteins in human skin fibroblasts. The purpose of this study was to investigate the expressions of type I collagen, MMP-1, Smad2/3, and TIMP-1 proteins in AF-343-treated human skin fibroblasts. Human skin fibroblasts were treated by various concentrations of AF-343 (0~2 mg/ml). The expressions of type I collagen, matrix metalloproteinase-1 (MMP-1), Smad2/3, and TIMP-1 proteins were analyzed by Western blot analysis. In addition, level of type I collagen mRNA was analyzed by CAT assay. Expression of type I collagen protein was increased in AF-343-treated human skin fibroblasts by dose and time-dependent manners. Consistent with this result, the expressions of phospho-Smad2/3 in skin fibroblasts were increased and MMP-1 expression was decreased by AF-343 treatment. TIMP-1 expression was not significantly changed in AF-343 treated skin fibroblasts. Extract of Taraxacum platycarpum (AF-343)-induced up-regulation of type I collagen expression was through increased expression of phospho-Smad2/3. These results were occurred combined with down-regulation of MMP-1 in skin fibroblasts. Taken together, this study indicated that AF-343 has property of the modulation of ECM in tissue as well as skin hydration and anti-inflammation.