• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.64-72
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• 2021

Renal cell carcinoma (RCC) is likely to metastasize to other organs, and is often resistant to conventional chemotherapies. Thymoquinone (TQ), a phytochemical derived from the seeds of Nigella sativa, has been shown to inhibit migration and metastasis in various cancers. In this study, we assessed the effect of TQ on the migratory activity of human RCC Caki-1 cells. We found that treatment with TQ reduced the proteolytic activity of matrix metalloproteinase-9 (MMP-9) in Caki-1 cells. TQ significantly repressed prostaglandin E2 (PGE2) production, its EP2 receptor expression as well as the activation of Akt and p38, the wellknown upstream signal proteins of MMP-9. In addition, treatment with butaprost, a PGE2 agonist, also induced MMP-9 activity and migration/invasion in Caki-1 cells. Moreover, pharmacological inhibitors of PI3K/Akt and p38 remarkably attenuated butaprost-induced Caki-1 cell migration and invasion, implying that activation of PI3K/Akt and p38 is a bridge between the PGE2-EP2 axis and MMP-9-dependent migration and invasion. Taken together, these data suggest that TQ is a promising anti-metastatic drug to treat advanced and metastatic RCC.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.1
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• pp.40-49
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• 2023

Objectives : This study was conducted to confirm the skin anti-aging effect of Chungpyesagan-tang(CPSGT) extract. Methods : We performed MMT assay to confirm the cytotoxicity of CPSGT. After inducing matrix metalloproteinase-1(MMP-1) with tumor necrosis factor-α(TNF-α), we investigated mRNA expression and protein secretion of MMP-1 by real-time RT-PCR and ELISA. In addition, we measured the protein expression of mitogen-activated protein kinases(MAPKs) and transcription factors by western blot. Results : CPSGT was not cytotoxic at 25-800㎍/㎖. The mRNA expression and protein secretion of MMP-1 decreased when treated with CPSGT. The protein expression of p-ERK, p-JNK, p-p38 was decreased by CPSGT. In addition, the protein expression of p-c-jun and p-NF-κB, which are transcription factors, were also decreased. Conclusion : This suggests that CPSGT can inhibit MMP-1 and thus be a potential anti-aging substance.

• 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.

• KSBB Journal
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• v.25 no.3
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• pp.265-270
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• 2010

Simvastatins are widely used to reduce endogenous cholesterol synthesis and improve hypercholesterolemia. Also, simvastatin have been shown to induce both angiogenic and angiostatic responses. In this study, It was attempted to resolve this controversy by studying the effects of simvastatin on the cell migration and invasion with the proteinases secretion and expression pattern. U-373-MG cells treated with low dose of simvastatin ($0.001{\sim}0.5\;{\mu}M$) showed the induction of migration and invasion compared with the addition of a control buffer. On the contrary, high dose of simvastatin ($1{\sim}20\;{\mu}M$) showed the reduction of migration and invasion compared with the addition of a control buffer. It was also showed that simvastatin-regulated migrative and invasive phenotypes were consistent with the secretion and expression pattern of matrix metalloproteinase-2 (MMP-2), MMP-9 and plasmin.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6829-6835
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• 2014

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4823-4827
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• 2014

Background: Since inconsistent results have been reported regarding the relation between the matrix metalloproteinase-2 (MMP-2) -1306C>T polymorphism and susceptibility for breast cancer, we performed a meta-analysis to investigate the issue. Materials and Methods: An internet search of PubMed and EMBASE was performed to identify eligible studies. Pooled odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated to evaluate any association between MMP-2 -1306C>T polymorphism and breast cancer susceptibility. Results: Nine case-control studies were included in the meta-analysis, involving 9,858 cases and 10,871 controls. Overall, there was no evidence of any association between the MMP-2 -1306C>T polymorphism and breast cancer susceptibility in different genetic models (T-allele vs C-allele: OR=0.95, 95%CI, 0.82-1.10, p=0.49; TT vs CC: OR=1.03, 95%CI, 0.90-1.19, p=0.66; TT+TC vs CC: OR=0.93, 95%CI, 0.78-1.10, p=0.38; TT vs TC+CC: OR=1.02, 95%CI, 0.89-1.17, p=0.77). In the subgroup analysis by ethnicity, CC was associated with a significant increase in breast susceptibility among Latin-Americans in the dominant model (OR=0.61, 95%CI, 0.40-0.93, p=0.02), but the association disappeared in other models. No significant association was observed among Europeans, East Asians and others in different genetic models. In the subgroup analysis by their source of controls, no significant association between MMP-2 -1306C>T polymorphism and breast cancer susceptibility was noted among population-based studies and hospital-based studies in different genetic models. Conclusions: The results of this meta-analysis suggest that MMP-2 -1306C>T polymorphism is not associated with breast cancer susceptibility, although the association among Latin-Americans in the dominant model was significant.

• Journal of Life Science
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• v.32 no.12
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• pp.938-946
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• 2022

This study aims to evaluate the effects of antioxidant activities, protein and mRNA expressions of matrix metalloproteinase (MMP) -1 and procollagen type I C-peptide (PIP) in 70% ethanol extract from Hydnocarpus anthelmintica Pierre (HE). DPPH and ABTS⁺ radicals scavenging assays were measured for antioxidant activities and HE had 73.5% and 74.4% of scavenging activities at 1,000 ㎍/ml concentration, respectively. And we investigated the inhibition of collagenase by HE, and the result was a 78.8% inhibition effect on concentrations of 1,000 ㎍/ml. In addition, an MTT assay was performed to confirm the toxicity of the CCD-986sk fibroblasts to the HE, and as a result, the cell viability rate was about 91.7% at a concentration of 50 ㎍/ml or less, and subsequent cell experiments were performed at a concentration of 50 ㎍/ml or less. We treated the cells with UVB (20 mJ/cm²) for stimulation, treated HE at various concentrations, and performed ELISA tests and RT-PCR experiments. And HE increased the PIP and mRNA in a dose-dependent manner and showed an expression rate of about 64.2% and 83.4%, respectively, at a concentration of 50 ㎍/ml compared with Cont (50.3% and 45.8%, respectively). And HE suppressed the MMP-1 protein and mRNA in a dose-dependent manner and showed a low expression rate of about 48.7% and 35.9%, respectively, at a concentration of 50 ㎍/ml. These results can be applied to developing anti-wrinkle materials for functional food and cosmetics with HE.

• Journal of agriculture & life science
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• v.50 no.2
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• pp.151-160
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• 2016

Inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. Sulforaphane, isolated from the Broccoli(Brassica oleracea var. italia) florets, inhibits the production of inflamatory cytokine. In the present study, we determined inhibitory effect of sulforaphane on Receptor activator of nuclear factor κB ligand(RANKL)-induced osteoclast formation. Sulforaphane inhibited the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase(TRAP), cathepsin K, matrix metalloproteinase 9(MMP-9), and calcitonin receptor in RANKL-induced RAW 264.7 macrophage. Also, sluforaphane inhibited the expression of osteoclast protein, such as TRAP, MMP-9, tumor necrosis factor receptor-associated factor 6(TRAF6) and transcription factor nuclease factor of activated T cells(NFAT)c1. Sulforaphane inhibited RANKL-induced activiation of nuclear factor kappaB(NF-kappaB) by suppression RANKL-mediated NF-kappaB transcriptional acitivation. We are confirmed that sulforaphane inhibits not only transcriptional activity of NF-kappaB but also expressions of the osteoclastogenesis factors(TRAP, cathepsin K, MMP-9, calcitonin, TRAF6) and trranscription factor NFATc1.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4751-4758
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• 2015

Echinodermata use saponins in chemical defense against pathogens and predators. The molecular mechanisms of antimetastatic effects of brittle star saponins are still unknown. The present study examined antioxidant capacity and invasive ability in HeLa carcinoma cells exposed to brittle star crude saponins. Discolorating methods with DPPH and ABTS and expression of SOD-2 with RT-PCR were used to estimate the antioxidant activity. The anti-invasive activity of extracted saponins was examined through adhesion of HeLa cells to extracellular matrix, wound healing and evaluation of the mRNA levels of MMP-2 and MMP-9 by real time-PCR. The results showed that extracted saponins had cytotoxicity against cervical cancer cells and ABTS and DPPH scavenging properties with $IC_{50}$ values of 604.5, $1012{\mu}g/ml$, respectively. Further, we found that, in wound healing assay, brittle star saponins could prevent invasion of HeLa cells in a concentration dependent manner. Furthermore, cell adhesion assay demonstrated blockage of cell attachment to extracellular matrix with an $IC_{50}$ concentration of $16.1{\mu}g/ml$. The significant dose dependent down regulation of MMP-2 and MMP-9 in treated cells demonstrated that isolated saponins can decline tumor metastasis in vitro. The brittle star saponins remarkably prevented cervical cancer invasion and migration associated with down regulation of matrix metalloproteinase expression. Therefore, saponins could be suggested as an anti-invasive candidate against cervical cancer and an antioxidant as well.

• Journal of Life Science
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• v.21 no.11
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• pp.1501-1510
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• 2011

In recent years novel potential pharmocological candidates have been looked for in animal, seaweed, sponge, fungi and marine bacteria resources. In this study, matrix metalloproteinases (MMPs) that play an important role in metastasis, arthritis, chronic inflammation and wrinkle formation were used as target enzymes to screen therapeutic agents. The inhibitory effects of several marine algae including green algae (5 species), red algae (18 species) and brown algae (4 species) methanolic extracts on MMPs were investigated in human dermal fibroblasts and human fibrosarcoma cell line (HT1080 cells) using gelatin zymography. In human dermal fibroblasts, the inhibition of MMP-2 was observed in Laurencia okamurae, Polysiphonia japonica, Grateloupia lanceolate and Sinkoraena lancifolia of red algae. In contrast, MMP-2 activation was enhanced in Enteromorpha compressa and E. linza of green algae, and Peltaronia bighamiae and Sargassum thunbergii of brown algae. In human fibrosarcoma cells, MMP-9 activation was decreased in the presence of S. thunbergii of brown algae, Polysiphonia japonica in red algae and E. compressa and E. linza of green algae. The interesting finding is that E. compressa and E. linza of green algae, and S. thunbergii of brown algae exhibited a positive effect on MMP-2 in normal cells, but a negative effect on MMP-9 in cancer cell lines. These results suggest that E. compressa and E. linza of green algae, and S. thunbergii of brown algae contain potential therapeutic ingredients for cancer treatment.