• Biomedical Science Letters
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• v.20 no.3
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• pp.103-110
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• 2014

Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They are multidomain proteins and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs). The uncontrolled regulation of MMPs is involved in various pathologic processes, such as tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Especially, matrix metalloproteinase-9 (MMP-9) is one of the metastasis-accelerating genes involved in metastasis of various types of human cancers. Here, we review the member of MMP family and discusses their domain structure and function, enzyme activation, the mechanism of inhibition by TIMPs. In particular, we focus the role of MMP-9 in relation to cancer metastasis.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.89-96
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• 2000

A human hepatoma cell line, Hep G2 cells are a reliable for the study of alcohol-induced hepatotoxicity. In this study, the author investigated the effect of an aqueous extract of Asparagus $cochinchinensis_{MERRIL}$ (Liliaceae) roots (ACAE) on ethanol (EtOH)-induced cytotoxicity in Hep G2 cells. ACAE dose-dependently inhibited the EtOH-induced tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ secretion. ACAE also inhibited the EtOH and $TNF-{\alpha}-induced$ cytotoxicity. Furthermore, the author found that ACAE inhibited the $TNF-{\alpha}-induced$ apoptosis of Hep G2 cells. These results suggest that ACAE may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5005-5006
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• 2015

Gastric cancer as one of the most common cancers worldwide has various genetic and environmental risk factors including Helicobacter pylori (H.pylori) infection. Recently, loss of a tumor suppressor gene named promyelocytic leukemia (PML) has been identified in gastric cancer. However, no mutation has been found in this gene in gastric cancer samples. Cag A H.pylori protein has been shown to exert post transcriptional regulation of some tumor suppressor genes. In order to assess such a mechanism for PML degradation, we performed in silico analyses to establish any interaction between PML and Cag A proteins. In silico interaction and docking studies showed that these two proteins may have stable interactions. In addition, we showed that imatinib kinase inhibitor can restore PML function by inhibition of casein kinase 2.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1877-1880
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• 2012

Breast cancer metastasis is the most common cause of cancer-related death in women. Thus, seeking targets of breast tumor cells is an attractive goal towards improving clinical treatment. The present study showed that CCL18 from tumor-associated macrophages could promote breast cancer metastasis via PITPNM3. In addition, we found that pachymic acid (PA) could dose-dependently inhibit migration and invasion of MDA-MB-231cells, with or without rCCL18 stimulation. Furthermore, evidence was obtained that PA could suppress the phosphorylation of PITPNM3 and the combination of CCL18 and PITPNM3. Therefore, we speculate that PA could inhibit breast cancer metastasis via PITPNM3.

• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.428-433
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• 2015

Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-${\kappa}B$ signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-${\kappa}B$ activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.463-469
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• 2000

Protein-polysaccharide fractions separated from nine Korean wild mushrooms were subjected to an in vitro screening test for lymphoblastogenic activity. Of these, PPLP, the protein-polysaccharide fraction of Lycoperdon pedicellatum, showed the most potent activity and were further investigated for its antitumor activity. When intraperitoneally injected into ICR mice once daily for six days at a dose of 30 mg/kg, PPLP strongly inhibited the growth of sarcoma 180 tumor cells, showing the inhibition ratio of 97.6%. PPLP also showed in vitro inhibitory activity on sarcoma 180 or leukemia L1210 at the concentration of 500 $\mu\textrm{g}$/$m\ell$ or higher. These results strongly suggest that PPLP might exert its antitumor activity through immunostimulation as well as inhibitory activity on the tumor cells.

• Development and Reproduction
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• v.26 no.3
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• pp.117-126
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• 2022

Bromodomain-containing protein 7 (BRD7) participates in many cellular processes and embryo development. BRD7 is down-regulated in various cancers and evidence of its tumor suppressor function has been accumulating. Here, we identified transforming stimulated clone 22 (TSC-22) as a novel BRD7 interacting protein and show its novel function as a positive regulator of BRD7. We found that TSC-22 expression potentiated the inactivation of the extracellular signal-regulate kinase (ERK) pathway by BRD7. Our data establishes TSC-22 as a modulator of BRD7 and unravels the molecular mechanisms that drive the synergistic tumor-suppressing effects of TSC-22 and BRD7. Our findings may open new avenues for developing novel molecular therapies for tumors exhibiting down-regulated BRD7 and/or TSC-22.

• IMMUNE NETWORK
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• v.3 no.1
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• pp.53-60
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• 2003

Background: The role of macrophages in tumor angiogenesis is known to be the production of angiogenic cytokines and growth factors including TNF-${\alpha}$. Recently, macrophage also can produce the INF-${\gamma}$ that is being studied to be involved in angiogenic inhibition. Thus, the importance of macrophages in tumor angiogenesis is might being an angiogenic switch. Thus, the hypothesis tested here is that TNF-${\alpha}$ can modulate the INF-${\gamma}$ production in the macrophages from tumor environment as a part of tumor angiogenic switch. Methods: Macrophages in tumor environment were obtained from the peritoneal cavity of C57BL/6 mice injected with B16F10 melanoma cell line for 6 or 11 days. $Mac1^+$-macrophages were purified using magnetic bead ($MACs^{TM}$; Milteny Biotech, Germany) and cultured with various concentrations of TNF-${\alpha}$ for various time points at $37^{\circ}C$. The supernatants were analyzed for IFN-${\gamma}$ or VEGF by ELISA kit (Endogen, Woburn, MA). Results: Residential macrophages from the peritoneal cavity did not respond to LPS or TNF-${\alpha}$ to produce INF-${\gamma}$. However, the cells from tumor environment produced IFN-${\gamma}$ as well as VEGF and upregulated by the addition of LPS or TNF-${\alpha}$. RT-PCR analysis revealed the external TNF-${\alpha}$-induced IFN-${\gamma}$ gene expression in the macrophages from tumor environment. Conclusion: The overall data suggest that the macrophages in tumor environment might have an important role not only in angiogenic signal but also in anti-angiogenic signal by producing related cytokines. And TNF-${\alpha}$ might be a key cytokine in tumor angiogenic switch.

• Advances in Traditional Medicine
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• v.5 no.4
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• pp.283-293
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• 2005

Our previous study showed that a novel synthetic shikonin derivative, 6-(1-hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) induced apoptosis. In the present study, we investigated its anti-metastatic activities as compared with shikonin because DMNQ S-52 was synthesized for overcoming weak points of shikonin such as high toxicity, low solubility and deleterious effects. DMNQ S-52 showed the weaker cytotoxicity $(IC_{50};\;12.3{\pm}1.6\;{\mu}M)$ against Lewis lung carcinoma (LLC) cells than that of shikonin $(IC_{50};\;4.2{\pm}1.1\;{\mu}M)$. DMNQ S-52, at non-toxic concentrations $(less\;than\;10\;{\mu}M)$, significantly inhibited the invasion and migration of LLC cells. DMNQ S-52 also significantly inhibited the production of MMP-9, MTl-MMP and uPAR. Moreover, daily i.p. administration of DMNQ S-52 at dose of 5 mg/kg in mice resulted in a potent inhibition of the primary tumor size of LLC in the lung as well as the metastasis of lymph nodes. These findings suggest that the DMNQ S-52 has therapeutic potential to inhibit metastasis via inhibition of MMP family and uPA/plasminogen system.

• Food Science and Biotechnology
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• v.17 no.5
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• pp.1106-1109
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• 2008

The anti-Helicobacter pylori activity, cytotoxicity, and anti-inflammatory activity of white ginseng extract (WGE) were investigated in vitro in this study. The antimicrobial effects of WGE toward H. pylori strains 52 J99, SSI, and 51 were tested using the disk diffusion method. Among these H. pylori strains, H. pylori 52 was the most sensitive, having the largest inhibition zone (19 mm), followed by J99, SSI, and 51. The zone of inhibition due to WGE increased significantly with increasing dosage. The cytotoxicity of WGE toward the human cancer cell lines A-549 (human lung carcinoma), HEC-1-B (human endometrial adenocarcinoma), HeLa (human uterin adenocarcinoma), and SW-156 (human kidney carcinoma) was measured using the 3-(4,5-dimethylthizol-2-yl)-2,5-diphenylate-tetrazolium bromide (MTT) assay. WGE exhibited an inhibitory effect on cell growth at 2.0 mg/mL for all tumor cell lines. An analysis of anti-inflammatory activity using the RAW 264.7 cell line showed that the inhibition of nitric oxide (NO) production increased as the WGE content increased. These results demonstrate the potential of WGE to be used as a health-promoting substance.