• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.591-598
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• 2012

Aim and background: MicroRNAs (miRNAs) are a class of naturally occurring small noncoding RNAs that regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or cleavage. The present study was conducted to study miRNAs in Egyptian breast cancer (BC) and their relation to metastasis, tumor invasion and apoptosis in addition to their association with the ER and PR statuses. Methods: Real Time RT-PCR was performed to identify the miRNA expression level of eight miRNAs and eight metastatic-related genes in 40 breast cancer samples and their adjacent non-neoplastic tissues. The expression levels of each miRNA relative to U6 RNA were determined using the $^{2-{\Delta}}CT$ method. Also, miRNA expression profiles of the BC and their corresponding ANT were evaluated. Results: The BC patients showed an up-regulation in miRNAs (mir-155, mir-10, mir-21 and mir-373) with an upregulation in MMP2, MMp9 and VEGF genes. We found down regulation in mir-17p, mir-126, mir-335, mir-30b and also TIMP3, TMP1 and PDCD4 genes in the cancer tissue compared to the adjacent non-neoplastic tissues. Mir -10b, mir -21, mir-155 and mir373 and the metastatic genes MMP2, MMP9 and VEGF were significantly associated with an increase in tumor size (P < 0.05). No significant difference was observed between any of the studied miRNAs regarding lymph node metastasis. Mir-21 was significantly over-expressed in ER-/PR-cases. Conclusion: Specific miRNAs (mir-10, mir-21, mir-155, mir-373, mir-30b, mir-126, mir-17p, mir-335) are associated with tumor metastasis and other clinical characteristics for BC, facilitating identification of individuals who are at risk.

• Korean Journal of Plant Resources
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• v.31 no.1
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• pp.16-23
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• 2018

Paeonia japonica is a perennial flowering plant used in traditional medicine therapy. The purpose of this study was to investigate the effect of water extract and solvent fractions obtained from P. japonica on anti-oxidative, anti-thrombin, anti-invasive and pro-apoptotic activities in YD-10B cells, human oral squamous carcinoma cell line. Water fraction revealed the highest extraction yield at 11.44% (w/w). Anti-oxidative activity was the highest in ethyl acetate fraction (85.13%). In the thrombin inhibitory activity test, ethyl fraction was the highest, with a value of 87.54%. Release and activation of MMP-2/pro-MMP-2 ratio in thrombin-treated YD-10B cells were significantly inhibited in the ethyl acetate fraction. At a concentration of $120{\mu}g/m{\ell}$ water extract and solvent fractions of P. japonica inhibited cell proliferation in YD-10B cells except water fraction. Pro-apoptotic effect on human oral squamous carcinoma cell using the Bax/Bcl-2 ratio analysis was higher in water extract than other fractions. These findings suggest that the ethyl acetate fraction of P. japonica potentiates a promising antioxidant, anti-thrombin and anti-invasive agents.

• The Journal of Korean Medicine
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• v.27 no.1 s.65
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• pp.229-239
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• 2006

Objectives : 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 extracelluar matrix. The purpose of this study was to investigate the effects of KHBJs for cartilage-protective effect in human and rabbit articular cartilage explants. Methods : The cartilage-protective effects of KHBJ were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMPs activity, and histological analysis in rabbit and human cartilage explants culture. Results : KHBJs significantly inhibited GAG and collagen release of rabbit and human cartilage explant in a concentration-dependent manner. Also, KHBJs inhibited MMP-3 and MMP-13 activities from IL-$1{\alpha}$-treated cartilage explants cultures. Histological analysis indicated that KHBJ004 reduced the degradation of the cartilage matrix compared with that of IL-$1{\alpha}$-treated cartilage explants. KHBJ004 had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Conclusions : These results indicate that KHBJs inhibits the degradation of proteoglycan and collagen through the downregulation of MMP-3 and MMP-13 activities without affecting the viability or morphology of IL-$1{\alpha}$-stimulated rabbit and human articular cartilage explants.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1793-1797
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• 2012

Objective: To analyze the capacity of neurotrophic artemin to promote the motility and invasiveness of MIA PaCa-2 pancreatic cancer cells. Methods: MIA PaCa-2 was cultured in vitro and studied using transwell chambers for motility and invasiveness on treatment with different concentrations of aArtemin or its receptor $GFR{\alpha}3$ were also determined. Expression of matrix metalloproteinase-2 (MMP-2) and epithelial cadherin (E-cadherin) was quantified using RT-PCR and Western blotting. Results: MIA PaCa-2 pancreatic cancer cell motility and invasiveness was significantly increased with artemin and its receptor $GFR{\alpha}3$ with dose dependence (P<0.01). MMP-2 production was also significantly increased (t = 6.35, t = 7.32), while E-cadherin was significantly lowered (t = 4.27, t = 5.61) (P <0.01). Conclusion: Artemin and its receptor $GFR{\alpha}3$ can promote pancreatic cancer cell motility and invasiveness and contribute to aggressive behavior. The mechanism may be related to increased expression of MMP-2 molecule and down-regulation of E-cadherin expression.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.94-94
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• 2019

황해쑥(Artemisia argyi H.Lev. & Vaniot)은 우수한 항염증 활성을 지닌 것으로 다양하게 보고 되었다. 그러나, 대표적인 염증 질환 중 하나인 골관절염에 미치는 영향은 현재까지 알려져 있지 않다. 따라서, 본 연구에서는 염증 유발 연골 세포 및 골관절염 유발 동물 모델에 미치는 황해쑥 효과에 대해 조사하였다. 첫째, interleukin 1 beta를 투여한 관절 연골 세포에 황해쑥 물 추출물을 투여한 후 metalloporeinase (MMP) -3 및 MMP-13의 발현을 mRNA 및 단백질 수준에서 분석 하였다. 또한, 내측 반월상 연골의 불안정화에 의해 유도 된 골관절염 마우스 모델을 사용하여 황해쑥 물 추출물의 골관절염 억제 효과를 분석 하였다. 세포 실험에서, 본 황해쑥은 MMP-3와 MMP-13의 mRNA 및 단백질 발현을 유의하게 억제하였다. 또한. 황해쑥 물 추출물을 투여한 실험 동물의 관절 조직을 Safranin O 염색을 실시하여 분석한 결과 연골 하 골판 두께의 감소 및 활막 염증 개선 효과가 관찰 되었다. HPLC를 이용한 성분 분석 결과, 황해쑥 물 추출물은 항염증 및 항관절염 활성을 가진 jaceosidin과 eupatilin을 함유하는 것으로 나타났다. 본 연구결과로부터 황해쑥은 골관절염의 치료 또는 예방에 유망한 소재로 개발될 수 있음을 시사한다.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.794-802
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• 2021

In this study we investigated the role and mechanism of cardamonin on IL-1β induced injury in OA. CHON-001 cells were treated with cardamonin and IL-1β and transfected with silencing nuclear factor erythroid 2-related factor 2 (siNrf2). Cell viability was detected by Cell Counting Kit-8 assay and flow cytometer assay was utilized for cell apoptosis assessment. IL-6, IL-8, TNF-α and Nrf2 mRNA expression was tested by qRT-PCR. Western blot was employed to evaluate MMP-3, MMP-13, Collagen II, Nrf2, NQO-1, NLRP3, Caspase 1 and apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) protein levels. In CHON-001 cells, IL-1β suppressed cell viability and Collagen II level while promoting cell apoptosis and expression of pro-inflammatory cytokines (IL-6, IL-8, TNF-α), MMPs (MMP-3, MMP-13), NQO-1, and NLRP3 inflammasome (NLRP3, Caspase 1 and ASC), with no significant influence on Nrf2. Cardamonin reversed the effect of IL-1β on cell viability, cell apoptosis, pro-inflammatory cytokines, MMPs, Collagen II, and NLRP3 inflammasome levels. In addition, cardamonin advanced Nrf2 and NQO-1 expression of CHON-001 cells. SiNrf2 reversed the function of cardamonin on IL-1β-induced cell apoptosis and expression of pro-inflammatory cytokines, Nrf2, NQO-1, and NLRP3 inflammasome in chondrocytes. Taken together Cardamonin inhibited IL-1β induced injury by inhibition of NLRP3 inflammasome via activating Nrf2/NQO1 signaling pathway in chondrocyte.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.1
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• pp.7-13
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• 2004

As a novel anti-wrinkle agent, 3,9-diferuloyl-6-oxopterocarpen (Tensolin-F$^{(R)}$) has been synthesized and its anti-aging effects have been investigated. In the present study, to investigate the relationship between aging and Tensolin-F$^{(R)}$, we examined its effect on scavenging activities of radicals and reactive oxygen species (ROS), in vitro inhibition activity of matrix-metalloproteinase (MMP) and expression of UVA-induced MMPs in human dermal fibroblasts (HDF). Tensolin-F$^{(R)}$ was found to show activities of scavenging radicals and ROS with the $IC_{50}$/ values of 0.2 mM and 0.95 mM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide radicals, respectively, in the xanthine/xanthine oxidase system. Fluorometric assays for the proteolytic activities of MMP-l (collagenase) were performed using fluorescent collagen substrates. Tensolin-F$^{(R)}$ inhibited the activities of MMP-l in a dose-dependent manner and the $IC_{50}$/ values calculated from semi-log plots were 0.025 mM. Also, UVA induced MMP-1 expression was reduced 85％ by treatment with Tensolin-F$^{(R)}$ at 0.8 uM, which was reduced dose-dependent manner. The results of clinical study showed that 4.8 mM Tensolin-F$^{(R)}$ treated group reduced wrinkle significantly compared with placebo treated group (P 〈 0.05). Taken together, these result suggest that Tensolin-F$^{(R)}$ act as an anti-wrinkle agent by taking effects to antioxidation and reducing UVA-induced MMP-l production.-l production.

• The Journal of Internal Korean Medicine
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• v.29 no.3
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• pp.543-553
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• 2008

Objective: The goal of this study was to determine the anti-asthma mechanism of SF on TNF-${\alpha}$ induced activation on A549 (human type II-like epithelial) cells. Using oligonucleotide microarray, we sought to establish the molecular mechanism of the protective effects of SF on A549 cells. Material & Methods : Cells were cultured in three different conditions: 1) negative control group was cultured in normal condition of DMEM, 2) positive control group was activated with TNF-${\alpha}$, IL-4. and IL-1${\beta}$, and 3) SF treated group was previously treated with 0.1${\mu}g/ml$ SF after TNF-${\alpha}$, IL-4. and IL-1 activation. Cells of positive control and SF treated groups were cultured for 30 min, 1hr, 3hr and 6hr. Results : The comparative analysis of the gene expression profile revealed that proinflammatory cytokines such as IL1F8, IL1F9, IL1R1. IL1RN, IL1RAPL1, IL8, TNFRSF4, TNFSF10c, TNFSF13, TRAF5, and TRAF7 and inflammation-related genes including MMP2, MMP11, MMP14, MMP15, MMP16, MMP19, MMP25, and MMP27 were down regulated with SF treatment. Cell adhesion molecule genes such as ITGB1, ITGBL1, selectin P ligand, selectin E, ICAM2, ICAM3, VCAM1, PECAM, FCER1G and MMP28 genes were also down-regulated in SF treated A549 cells. Conclusion : These results suggest that the anti-asthmatic effects of SF could be mediated by regulating specific genes related with cell adhesion, proinflammatory cytokine and inflammation-related genes in A549 cells.

• Korean Journal of Food Science and Technology
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• v.52 no.4
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• pp.385-395
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• 2020

This study examined the effect of 3,4-dihydroxytoluene (DHT) on UVB-induced photoaging and determined its molecular mechanisms, using HaCaT human keratinocytes and SKH-1 hairless mice. DHT suppressed UVB-induced matrix metalloproteinase-1 (MMP-1) expression in HaCaT cells. In vivo data from mouse skin supported that DHT decreased UVB-induced wrinkle formation, epidermal thickness, and matrix metalloproteinase-13 (MMP-13) expression. DHT appeared to exert its anti-aging effects by suppressing UVB-induced Raf-1 kinase activity and subsequent attenuation of UVB-induced phosphorylation of MEK, ERK, and p90RSK in HaCaT cells. In vitro and in vivo pull-down assays revealed that DHT bound with Raf-1 in ATP-noncompetitive manner. Overall, DHT appears to anti-photoaging effects in vitro and in vivo through the suppression of Raf-1 kinase activity and may have potential as a treatment for the prevention of skin aging.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2269-2272
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• 2013

Matrix metalloproteinases (MMPs) degrade various components of the extracellular matrix and functional polymorphisms in encoding genes may contribute to genetic susceptibility to many cancers. Up to now, associations between MMP-7 (-181A>G) and digestive system cancer risk have remained inconclusive. To better understand the role of the MMP-7 (-181A>G) genotype in digestive cancer development, we conducted this comprehensive meta-analysis encompassing 3,518 cases and 4,596 controls. Overall, the MMP-7 (-181A>G) polymorphism was associated with higher digestive system cancer risk on homozygote comparison (GG vs. AA, OR=1.21, 95% CI = 1.12-1.60) and in a dominant model (GG/GA vs. AA, OR=1.16, 95% CI =1.03-1.46). On subgroup analysis, this polymorphism was significantly linked to higher risks for gastric cancer (GG vs. AA, OR=1.22, 95% CI = 1.02-1.46; GA vs. AA, OR=1.82, 95% CI =1.16-2.87; GG/GA vs. AA, OR=1.13, 95% CI =1.01-1.27; GG vs. GA/AA, OR= 1.25, 95% CI = 1.06-2.39. We also observed increased susceptibility to colorectal cancer and esophageal SCC in both homozygote (OR = 1.13, 95% CI = 1.06-1.26) and heterozygote comparisons (OR = 1.45, 95% CI = 1.11-1.91). In the stratified analysis by controls, significant effects were only observed in population-based studies (GA vs. AA, OR=1.16, 95% CI=1.08-1.50; GA/AA vs. GG, OR=1.10, 95% CI=1.01-1.72). According to the source of ethnicity, a significantly increased risk was found among Asian populations in the homozygote model (GG vs. AA, OR=1.40, 95% CI=1.12-1.69), heterozygote model (GA vs. AA, OR=1.26, 95% CI=1.02-1.51), and dominant model (GG/GA vs. AA, OR=1.18, 95% CI=1.08-1.55). Our findings suggest that the MMP-7 (-181A>G) polymorphism may be a risk factor for digestive system cancer, especially among Asian populations.