• Bulletin of the Korean Chemical Society
• /
• v.13 no.2
• /
• pp.155-157
• /
• 1992

Extensive search over the energy surface of bicyclo[4.2.2]decapentaene with MMP2 molecular mechanics method and AM1 semiempirical MO method revealed only one, deep energy minimum structure, which corresponds to 1. The alternative structure 2 could not be identified as a stationary point. Although the deviation of benzenoid ring from planarity is large in the energy minimum structure (${\phi} = 26^{\circ}$(MMP2), $37^{circ}$ (AM1)), the bond lengths show no severe alternation.

• Journal of Life Science
• /
• v.25 no.9
• /
• pp.1000-1006
• /
• 2015

α-Asarone is the main component of Acorus gramineus, which is a widely used oriental traditional medicine. A. gramineus is known to have a variety of medicinal effects, such as anti-gastric ulcer, antiallergy and antioxidant activity. It is also known to inhibit the release of histamine. However, the mechanism of its action remains unclear in humans. In this study, the effects of α-asarone on matrix metalloproteinase (MMP) and its antioxidant effect in a cell-free system were examined in HT1080 cells. In an MTT assay, the effect of α-asarone on cell viability showed no cytotoxicity below 16 μM. In an antioxidant assay, α-asarone increased reducing power in a dose-dependent manner but not the scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. In addition, α-asarone exhibited the protective effect against DNA oxidation induced by hydroxyl radicals produced by the Fenton reaction. Furthermore, in a gelatin disk assay, α-asarone enhanced collagenase activity. It also increased the activities of MMP-2 and MMP-9 stimulated by phorbol 12-myristate 13-acetate (PMA) in a gelatin zymography. On the other hand, the activity of MMP-9 stimulated by phenazine methosulfate (PMS) but not that of MMP-2 was increased in the presence of α-asarone. These findings suggest that α-asarone could be a candidate for the prevention and treatment of pathological diseases related to oxidative stress and MMPs.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.5981-5984
• /
• 2012

Background: Numerous studies have investigated the association of matrix metalloproteinase 1 (MMP1) rs1799750 single nucleotide polymorphism with lung cancer susceptibility, but the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate any possible association. Methods: We searched publications from MEDLINE, EMBASE and CNKI databases which assessed links between the MMP1 rs1799750 polymorphism and lung cancer risk. We calculated the pooled odds ratio (OR) and its 95% confidence interval (95%CI) using either fixed-effects or random-effects models. Results: The meta-analysis was based on 9 publications encompassing 4,823 cases and 4,298 controls. The overall results suggested there was a significant association between the MMP1 rs1799750 polymorphism and lung cancer risk (1G vs. 2G: OR = 0.83, 95%CI = 0.73-0.94; 1G1G vs. 2G2G: OR = 0.73, 95%CI = 0.59-0.92; 1G1G vs. 1G2G/2G2G: OR = 0.87, 95%CI = 0.79-0.97; 1G1G/1G2G vs. 2G2G: OR = 0.78, 95%CI = 0.64-0.95). In the subgroup analysis by ethnicity, the association was still obvious in Asians (all P values < 0.05), but there was no association in Caucasians (all P values > 0.05). Conclusions: The MMP1 rs1799750 polymorphism is associated with decreased lung cancer risk, and a race-specific effect may exist in this association.

• Journal of Life Science
• /
• v.26 no.5
• /
• pp.584-591
• /
• 2016

Saururus chinensis is a perennial plants, its flavonoid compound is known to exhibit anti-oxidative activity. This study was aimed to investigate the effect of Water Extract and Solvent Fractions of Saururus chinensis on antioxidant, anti-inflammatory and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities. Plant samples were fractionated into hexane, CHCl₃, ethyl acetate, butanol, and water fractions, and each of these was assayed individually. The water fraction showed the highest extraction yield at 9.25%(w/w). Anti-oxidative activity was analyzed by DPPH assay. Cell viability was detected by the MTS assay. Anti-inflammatory activity was assayed by the nitric oxide (NO) production in mouse macrophage Raw 264.7 cells. The activity and mRNA expression of MMP-2 and MMP-9 in human oral squamous carcinoma YD-10B cells were examined by zymography and RT-PCR. As results, MMP-2/-9 activation was increased in PMA induced YD-10B cells. In PMA-treated YD-10B cells, the increased mRNA expression and protein activation of MMP-2/-9 were significantly inhibited in the ethyl acetate fraction. The ethyl acetate fraction showed the highest anti-oxidative activity at 73.38%. The ethyl acetate fraction at non-cytotoxic concentrations significantly exhibited the anti-inflammatory activity of Raw 264.7 cells in dose-dependent manner. In conclusion, these findings demonstrate that the ethyl acetate fraction obtained from a chinensis water extract potentiates a promising therapeutic anti-invasive agent and, therefore, as an anti-cancer drug for cancer prevention and therapy in oral cancer.

• Tuberculosis and Respiratory Diseases
• /
• v.52 no.2
• /
• pp.107-116
• /
• 2002

Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.

• Tuberculosis and Respiratory Diseases
• /
• v.56 no.3
• /
• pp.289-296
• /
• 2004

Background : Mucus hypersecretion in the patients with airway diseases represents poor prognosis as well as discomfort. However, there is no known therapy for its effective control. One important component of mucus is mucin, a glycosylated protein, which endows mucus with viscosity. We studied whether a proteinase has a role in mucin secretion and if so, which. Methods : (1) Inhibition of mucin secretion Group-specific proteinase inhibitors were tested to evaluate whether a proteinase belonging to a group of proteinases plays a role in mucin secretion. Phenylmethylsulfonyl fluoride(PMSF, a serine proteinase inhibitor), E-64(a cysteine proteinase inhibitor), Pepstatin(an aspartic proteinase inhibitor) and 1, 10-Phenanthroline(a metalloproteinase inhibitor) were treated into the Calu-3 cell line for 24 hours. The enzyme linked immunoabsorbant assay(ELISA) for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with a control. (2) Stimulation of mucin secretion Matrix metalloproteinase-9(MMP-9), MMP-12 and TACE(TNF-alpha converting enzyme), which are known to be related with airway diseases, were used to be treated into Calu-3 for 24 hours. ELISA for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with the controls. Results : (1) PMSF($10^{-4}M$), E-64($10^{-4}M$), Pepstatin($10^{-6}M$) and 1, 10-Phenanthroline($10^{-4}M$) reduced the MUC5AC secretion by $1{\pm}4.9%$(mean${\pm}$standard deviation; P=1.0 compared with the control), $-6{\pm}3.9%$(P=0.34), $-13{\pm}9.7%$(P=0.34) and $41{\pm}8.2%$(P=0.03), respectively. (2) The amounts of MUC5AC secretion stimulated by MMP-9(250ng/ml), MMP-12(100ng/ml) and TACE(200ng/ml) were $103{\pm}6%$(P=0.39), $102{\pm}8%$(P=1.0) and $107{\pm}13%$(P=0.39), respectively, compared with the controls. Conclusion : Metalloproteinase(s) is (are) suggested to play a role in mucin secretion. It appears that metalloproteinases, other than MMP-9, MMP-12 or TACE, affect the mucin secretion in this in vitro model.

• The Journal of the Korea Contents Association
• /
• v.20 no.6
• /
• pp.124-130
• /
• 2020

The present study investigated the anti-proliferate and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities of combined treatment with cisplatin and ethyl acetate fractions of Paeonia japonica. Cell Proliferation was detected by the MTS assay and the activity and mRNA expression of MMP-2/-9 were examined by zymography and RT-PCR. As results, cisplatin or p. japonica treatment of YD-10B cells resulted in a dose-dependent inhibition of cell growth. Also, the viability of YD-10B cells treated with combination of 200 μM cisplatin and 50 ㎍/ml p. japonica was inhibited to 50% in compared with the cisplatin alone. In PMA-treated YD-10B cells, co-treatment of 200 μM cisplatin with 50 ㎍/ml p. japonica significantly inhibited mRNA expression and protein activation of MMP-2/-9. Therefore, This study suggest that the combination treatment of cisplatin and p. japonica potentiates a promising anti-invasive agent and has more potential anti-cancer drug for oral cancer therapy than cisplatin alone.

• YAKHAK HOEJI
• /
• v.48 no.6
• /
• pp.358-363
• /
• 2004

Matrix metalloproteinases (MMPs) are known to play an important role in photoaging by mediating the degradation of extracellular matrix proteins. In this study, to develop a n ew anti-aging agent, we investigated the antioxidant activity and the inhibitory effect of Melothria heterophylla extract on expression of MMP-1 in UVA-irradiated human dermal fibroblasts and MMP-1 activity. The M.heterophylla extract was found to scavenge radicals and reactive oxygen species (ROS) with the $SC_{50}$ values of $13{\mu}g/ml$ against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and $20{\mu}g/ml$ against superoxide radicals in the xanthine/xanthine oxidase system, respectively. UVA-induced MMP-1 expression was reduced about 80% by $100{\mu}g/ml$ of the M.heterophylla extract but MMP-1 Mrna expression was not inhibited. Therefore, we conclude that the M.heterophylla extract significantly inhibits MMP-1 expression at the protein level. Also, the M.heterophylla extract inhibited MMP-1 activity in a dose dependent manner. From these results, we suggest that the M.heterophylla extract can be used as a new anti-aging agent by antioxidant activity, regulation of UVA-induced MMP-1 production, and inhibition of MMP-1 activity.

• Journal of Periodontal and Implant Science
• /
• v.33 no.2
• /
• pp.277-288
• /
• 2003

It has been suggested that increased number and activity of phagocytes in periodontitis lesion results in a high degree of reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide, nitric oxide and peroxynitrite. There are few reports on the relationship between ROS and MMPs expressions in gingival fibroblast. We studied to elucidate whether and how ROS, especially nitric oxide affects the MMP expression. Human gingival fibroblasts and HTl080 cells (human fibrosarcoma sell line as reference) were grown in DMEM supplemented with 10 mM HEPES, 50 mg/L gentamicin, and 10% heat inactivated fetal bovine serum with addition of various reactive oxygen species (ROS). Culture media conditioned by cells were examined by gelatin zymography. HT1080 cells expressed proMMP-2 and proMMP-9, but human gingival fibroblasts (HGF) produced only proMMP-2. Hydrogen peroxide upregulated MMP-9 expression in HT1080 cells, whereas in human gingival fibroblast SNP treatment showed marked increase in MMP-2 level compared to other ROS. These results suggest that the effects of ROS on MMPs expressions are cell-type specific. RT-PCR for MMP-2 and TIMP-2 m-RNA were performed using total RNA from cultured cells under the influence various kinase inhibitors. In HT1080 cells, treatment with FPTI III (Ras processing inhibitor) and LY294002 (PI3-kinase inhibitor) resulted in inhibition of MMP-2 and MMP-9 expressions, suggesting that Ras/P13-kinase pathway is important for MMPs expression in HT1080 cells. In gingival fibroblasts, treatment with FPTI III and PDTC (NF-kB inhibitor) showed marked decrease in MMP-2 regardless of the of SNP , suggesting that Ras/NF-kB could be the key pathway for NO-induced MMP-2 expression in gingival fibroblasts. This study showed that ROS, especially nitric oxide, could be the critical mediator of periodontal disease progression through control of MMP-2 expression in gingival fibroblasts possibly via Ras/NF-kB pathway.

• Korean Journal of Environmental Biology
• /
• v.27 no.1
• /
• pp.58-65
• /
• 2009

The chemopreventive effects of naringenin derived from citrus on tumor migration and the possible mechanisms involved in this protection were investigated in HT-1080 tumor cells. In this study, we found that naringenin reduced phorbol 12-myristate 13-acetate (PMA)-enhanced matrix metalloproteinases (MMP)-9 activation in a dose-dependant manner and further inhibited HT-1080 cell migration. In addition, naringenin suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of nuclear factor $\kappa$B (NF-$\kappa$B) activation and activator protein-1 (AP-1) translocation without changing tissue inhibitor of metalloproteinase (TIMP)-1 level. Therefore, our results suggested that the inhibitory effects of naringenin on MMP-9 activation, relation of tumor migration in vitro possibly involve mechanisms related to its ability to suppress PMA-enhanced MMP-9 gene and protein expression through NF-$\kappa$B activation and AP-1 translocation. Overall, naringenin may be a valuable anti-invasive drug candidate for cancer therapy.