• Korean Journal of Food Science and Technology
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• v.53 no.3
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• pp.304-312
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• 2021

The present study aimed to develop new physiologically active ingredients from Angelica gigas. The polysaccharides purified from A. gigas, AGE-2c-I, showed potent anti-complementary activity in a dose-dependent manner. C₃ activation products were identified through crossed immuno-electrophoresis using anti-human C₃ antibodies and the anti-complementary activity of AGE-2c-I under Ca⁺⁺-free conditions suggests that AGE-2c-I may induce complementary activation via both alternative and classical pathways. In addition, AGE-2c-I augmented the production of various cytokines, such as interleukin (IL)-6, IL-10, IL-12, and tumor necrosis factor-α, by peritoneal macrophages. Furthermore, intravenous (i.v.) administration of AGE-2c-I dose-dependently enhanced natural killer cell cytotoxicity against YAC-1 lymphoma. In experimental lung metastasis, prophylactic i.v. administration of AGE-2c-I inhibited lung metastasis by 58% at 100 ㎍/mouse. From the above results, we suggest that AGE-2c-I purified from A. gigas has potent immune system-stimulating activities, and is a potentially promising food ingredient beneficial to human health.

• The Journal of Internal Korean Medicine
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• v.37 no.1
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• pp.16-25
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• 2016

Objectives: Gilgyung-tang (GGT) has been used as one of the main multi-herb formulas to treat “Peo-ong” (lung abscess). In this study, we investigated the inhibitory effects of water extracts of GGT on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, in human bladder cancer 5637 cells.Methods: Effects on cell viability were quantified using an MTT assay. To analyze the anti-metastatic effects, we conducted a wound healing migration assay, an in vitro invasiveness assay, and a measurement of the transepithelial electrical resistance (TER). The expression of protein and mRNA were measured by Western blotting and real-time polymerase chain reaction (RT-PCR), respectively.Results: GGT markedly inhibited the cell motility and invasiveness of 5637 cells within the concentration range that was not cytotoxic. The inhibitory effects of GGT on cell invasiveness were associated with tightening of the tight junctions (TJs), which was demonstrated by an increase in the TER. The RT-PCR and Western blotting results indicated that GGT decreased the levels of claudin proteins. GGT also inhibited the activity and expression of matrix metalloproteinase (MMP)-2 and -9 and simultaneously increased the levels of tissue inhibitor of metalloproteinase-1 and -2.Conclusions: Our findings suggest that GGT reduces both the migration and the invasion of 5637 cells by modulating the activity of TJs and MMPs.

• YAKHAK HOEJI
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• v.48 no.3
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• pp.189-196
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• 2004

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) playa key role in tumor invasion and metastasis. As an inhibitor of MMP-2, TIMP-2 is known to block both the invasive and metastatic behavior of cancer cells, and decrease tumor growth activity. We performed this study to investigate the effects of TIMP-2 over-expression induced by retroviral mediated gene transfer in vitro and in vivo. The human colon cancer cell line SW480 was transfected with the retroviral vector encoding TIMP-2. The effects of TIMP-2 over-expression were analyzed by invasion assay and gelatinase activity test in colon cancer cells and tumorigencity in nude mice. In evaluation of the transfection efficiency of the retroviral vector encoding TIMP-2 in colon cancer cells, we confirmed up-regulation of TIMP-2 expression dependent on the time of cell culture. In addition, inhibition of MMP-2 expression in SW480/TIMP-2 was shown by gelatin zymography. In the in vitro invasion assay SW480/TIMP-2 inhibited the invasiveness on matrigel coated with collagen. To determine whether TIMP-2 can modulate in vivo tumorigenicity and metastasis, SW480/TIMP-2 cells were injected subcutaneously in nude mice. The tumor mass formation of SW480/TIMP-2 cells in nude mice was markedly decreased compared to nontransfected cancer cells. These results showed that colon cancer cells transfected with the retroviral vector encoding TIMP-2 inhibits the invasiveness in vitro and tumorigenicity in vivo.

• Nutrition Research and Practice
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• v.3 no.4
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• pp.259-264
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• 2009

We examined the inhibitory effects of loquat methanol extract on the adhesion, migration, invasion and matrix metalloproteinase (MMP) activities of MDA-MB-231 human breast cancer cell line. Cells were cultured with DMSO or with 10, 25, or 50 ${\mu}g/ml$ of loquat methanol extract. Both leaf and seed extracts significantly inhibited growth of MDA-MB-231 cells in a dose-dependent manner, although leaf extract was more effective. Adhesion and migration were significantly inhibited by loquat extracts in a dose-dependent manner. Loquat extract also inhibited the invasion of breast cancer cells in a dose-dependent manner and leaf extract was more effective than seed extract. MMP-2 and MMP-9 activities were also inhibited by loquat extract. Our results indicate that methanol extracts of loquat inhibit the adhesion, migration and invasion of human breast cancer cells partially through the inhibition of MMP activity and leaf extract has more anti-metastatic effects in cell based assay than seed extract. Clinical application of loquat extract as a potent chemopreventive agent may be helpful in limiting breast cancer invasion and metastasis.

• Journal of Life Science
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• v.31 no.11
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• pp.980-986
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• 2021

Natural products have always been an attractive source in terms of novel anti-metastatic compounds which can hinder MMP expression and activity. Corydalis heterocarpa is a salt marsh plant found in the seashores throughout Korea. Its yellow flowers and spikes have been an ingredient in folk medicine to treat spasm and contractions. The present study assessed the potential of different solvent-based fractions from the crude extract of Corydalis heterocarpa (CHE), a halophyte with reported bioactivities, to suppress the PMA-induced MMP expression in human fibrosarcoma HT-1080 cells. The solvent fractions which were named after the solvent used for fractionation (n-hexane, 85% aqueous (aq.) methanol (MeOH), n-butanol (BuOH), and H₂O were shown to inhibit the both elevated mRNA and protein expression levels of MMP-2 and MMP-9 and simultaneously relieved the suppression on the expression of the endogenous MMP inhibitors TIMP-1 and TIMP-2. Results indicated that the CHE fractions might intervene with the PMA-induced activation of the MAPK signaling which is the upstream activator of MMP overexpression. Among tested samples, 85% aq. MeOH and n-hexane fractions of CHE was determined to be the most active and future studies to isolate the bioactive substances responsible for the regulation of the MMP expression are, therefore, urged. In conclusion, C. heterocarpa was shown to be a potential source of anti-metastatic compounds and n-Hexane and MeOH fractions might yield lead molecules to develop novel MMP inhibitors.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.211-224
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• 2002

Background and Objective : In order to investigate the effects of Gilgyunglwedok-tang (GRT) on antitumor activity and antimetastatic activity, studies were done experimentally. Materials and Methods : Experimental studies were perfonned for the cytotoxic effect on BALB/c mouse lung fibroblast cells, the proliferating effect of splenic lymphocyte, the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclear cells (PBMCs), the cytotoxic effect on A549, SK-OV-3, SK-MEL-2, MCF-7 cells, the inhibitory effect on the activity of DNA topoisomerase I, the T/C% in ICR mice bearing S-180, the inhibitory effect of Cell adhesive of A549 Cells and SK-OY-3 Cells to complex extracellular matrix, the inhibitory effect on lung colonies, the change of lung tissue, the antiangiogenic activity, and the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line. Results and Conclusion : The results were obtained as follows : 1. In the cytotoxic effect on BALB/C mouse lung fibroblast Cell, GHT didn't show the significant cytotoxic effect on BALB/C mouse lung fibroblast cell compared to the control group. 2. In thymidine uptake assay, GHT showed the significant proliferating effect of splenic lymphocyte in proportion to the concentration. 3. In the expression of CD3e/CD4, CD3e/CD8, and B220 in peripheral blood mononuclea cells (PBMCs) of mice, GRT had no significant change to the normal group in CD4. However, GRT showed an increase to the normal group in CD8 and GHT in the only $1\mu\textrm{g}/ml$ category showed an increase to the normal group in B220. 4. In the cytotoxic effect of GRT on A549, SK-OY-3, SK-MEL-2 and MCF-7 cells, there was no significant cytotoxic effect compared to the control group. 5. In the inhibitory effect on the activity of DNA topoisomerase I, GHT in the $10\mu\textrm{g}/ml$ category showed the inhibitory effect on the activity of DNA topoisomerase I in proportion to the concentration. 6. In the T/C% in ICRmice bearing S-180, GHTtreated group showed 123.7% of T/C% compared to the control group. 7. In the inhibitory effect of cell adhesive of A549 Cells and SK-OV-3 Cells to complex extracellular matrix, GRT in the only $100\mu\textrm{g}/ml$ category showed the significant inhibitory effect compared to the control group. 8. In the inhibitory effect on lung colonies, GHT showed the significant inhibitory effect on lung colonies compared to the control group. 9. In the change of lung tissue, GHT showed a significant decrease of lung cancer growth, interalveolar fibrosis and hyaline material compared to the control group. In the development of lymphocyte around lung cancer cells and lung parenchymal, GHT showed the significant inducement efficacy compared to the control group. 10. In CAM assay, the antiangiogenic activity of GHT showed 30%. 11. In the effect on MMP-2 and MMP-9 gene expression in the RT1080 cell line, GHT had no significant inhibitory effect on MMP-2 and MMP-9 gene expression compared to the control group. According to the above results, it could be suggested that GHT has an antitumor activity and antimetastatic activity.

• Journal of Korean Traditional Oncology
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• v.11 no.1
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• pp.75-93
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• 2006

Jiaweicitaowan (JWCTW) has been used to inhibit recurrence and metastasis of cancer in clinical practice. Further study has shown its anti-metastatic and anti-angiogenic effects. By applying in vitro and in vivo anti-angiogenic evaluation model, the author assayed the each ingredients of JWCTW. The author performed the following experiments and the results are listed as below: Cell viability assay showed that the viability was almost identical between that of the control and that of the ingredients extract 40 ${\mu}g/m{\ell}$ treated, except of hexane fraction of Curcumae Radix (40 ${\mu}g/m{\ell}$, 2.0% of control), ethylacetate fraction (40 ${\mu}g/m{\ell}$, 26.7%), butanol fraction (20 ${\mu}g/m{\ell}$, 87.2%; 40 ${\mu}g/m{\ell}$, 12.5%) of Cremastrae appendiculatae Tuber, water fraction of Persicae Semen (40 ${\mu}g/m{\ell}$, 82.7%), ethylacetate fraction of Hippocampus (40 ${\mu}g/m{\ell}$, 85.3%). The results of gelatin zymogram assay showed that the ingredients of JWCTW decreases the gelatinolytic activity of MMP-9 from ECV304, at the concentration of 10 ${\mu}g/m{\ell}$. In in vitro invasion assay, the ingredients of JWCTW effectively inhibited the invasion of cancer cells as compared with the control (+PMA) groups. In capillary-like tube formation assay, the hexane and ethylacetate fractions of Curcumae Radix, Cremastrae appendiculatae Tuber and Persicae Semen showed the dramatic inhibition effects on tube formation of ECV304 at the concentration of 40 ${\mu}g/m{\ell}$. In ex vivo rat aortic ring assay, the hexane and ethylacetate fractions of Curcumae Radix, Cremastrae appendiculatae Tuber and Persicae Semen showed the inhibition effects on angiogenesis of rat aorta at the concentration of 40 ${\mu}g/m{\ell}$. According to the above research, the anti-angiogenic effects of the ingredients of JWCTW was proved and it suggested that the more effective prescription for anti angiogenesis could be developed.

• Journal of Life Science
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• v.24 no.6
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• pp.700-706
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• 2014

Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.224-230
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• 1998

This study showed the anti-invasive activity of ginseng components, panaxadiol (PD) and panamatrlol (PT) on the highly metastatic HT1080 human flbrosarcoma cell line. PD and PT reduced tumor cell invasion through a reconstitute basement membrane in the transwell chamber. A significant down regulation of MMP-9 by PD and PT was detected by northern blot analysis. However, MMP-2 was constantly expressed. Quantitative gelatin based zymography confirmed a marked reduced expression of MMP-9 but not MMP-2 in the treatment of PD and PT. Since the chemical structures of PD and PT are very similar to that of dexamethasone, a synthetic glucocorticoid, it was investigated whether PD and PT act through GR. Western blot analysis and immunocytochemistry showed that PD and PT increased the GR fraction in the nucleus. These results suggest that ursolic acid may induce repression of MMP-9 by stimulating the nuclear translocation of GR and hence inhibiting the activity of AP-1 to TPA-responsible element of MMP-9 promoter region. In conclusion, we suggest that CR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT 1080 cells.

• IMMUNE NETWORK
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• v.6 no.3
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• pp.154-162
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• 2006

Background: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. Methods: B16F10 melanoma cells ($5{\times}10^4$/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. Results: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: $2.667{\pm}0.184,\;2.500{\pm}0.463,\;2.000{\pm}0.286,\;1.500{\pm}0.286,\;1.667 {\pm}0.297$ for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-${\gamma}$ secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate ($2,643.3{\pm}5,89.7,\;8,561.5{\pm}2,204.9.\;6,901.2{\pm}141.1pg/1{\times}10^6$ cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. Conclusion: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.