• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.4
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• pp.314-320
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• 2001

Matrix metalloproteinases have long been viewed as ideal candidates for proteinases that enables tumor cells to permeated basement membrane defenses and invade surrounding tissue. There is growing evidence that the MMPs have an expanded role, as they are important for the creation and maintenance of a microenvironment that facilitates growth and angiogenesis of tumors at primary and metastatic sites. MT-MMPs are not secreted but instead remaining attached to cell surfaces. Although not all of the MT-MMPs are fully characterized, MT-MMPs have important role in localizing and activating secreted MMPs. The MMP genes are transcriptionally responsive to a wide variety of oncogene, growth factors, cytokine, and hormones. Currently, a number of MMP inhibitors are being developed and some have reached clinical trials as anti-metastatic or anti-cancer therapies. MT1-MMP is involved in the activation of proMMP-2. MT1-MMP is significant not only as a tumor marker but as a new target for chemotherapy against cancer. The purpose of this study was to evaluate the effects of protein kinase C inhibitor(genistein) on the proliferation of HT1080 and expression of MT1-MMP mRNA. Human fibrosarcoma cell line HT1080 was cultured and divided 2 groups. The experimental group was treated with $100{\mu}M$ genistein and incubated 12h, 24h for $[3^H]-thymidine$ uptake assay and northern hybridization individually. And the control group was treated with same amount of PBS for the above procedures. $[3^H]-thymidine$ incorporation was measured with ${\beta}$ ray detector. And RT-PCR and northern blotting for MT1-MMP mRNA was performed. The results were as follows 1. $[3^H]-thymidine$ uptake was reduced in experimental group with statistical significance. 2. MT1-MMP mRNA expression was significantly reduced in experimental group. These results showed that protein kinase C inhibitor (genistein) inhibited proliferation of HT1080 and almost completely blocked transcription of MT1-MMP mRNA. So, it is possible to use the protein kinase inhibitor (genistein) as anti-metastatic and anti-proliferative agent.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6605-6611
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• 2013

Background: WEE1 is a G2/M checkpoint regulator protein. Various studies have indicated that WEE1 could be a good target for cancer therapy. The main aim of this study was to asssess the tumor suppressive potential of WEE1 silencing in two different breast cancer cell lines, MCF7 which carries the wild-type p53 and MDA-MB468 which contains a mutant type. Materials and Methods: After WEE1 knockdown with specific shRNAs downstream effects on cell viability and cell cycle progression were determined using MTT and flow cytometry analyses, respectively. Real-time PCR and Western blotting were conducted to assess the effect of WEE1 inhibition on the expression of apoptotic (p53) and anti-apoptotic (Bcl2) factors and also a growth marker (VEGF). Results: The results showed that WEE1 inhibition could cause a significant decrease in the viability of both MCF7 and MDA-MB-468 breast cancer cell lines by more than 50%. Interestingly, DNA content assays showed a significant increase in apoptotic cells following WEE1 silencing. WEE1 inhibition also induced upregulation of the apoptotic marker, p53, in breast cancer cells. A significant decrease in the expression of VEGF and Bcl-2 was observed following WEE1 inhibition in both cell lines. Conclusions: In concordance with previous studies, our data showed that WEE1 inhibition could induce G2 arrest abrogation and consequent cell death in breast cancer cells. Moreover, in this study, the observed interactions between the pro- and anti-apoptotic proteins and decrease in the angiogenesis marker expression confirm the susceptibility to apoptosis and validate the tumor suppressive effect of WEE1 inhibition in breast cancer cells. Interestingly, the levels of the sensitivity to WEE1 silencing in breast cancer cells, MCF7 and MDA-MB468, seem to be in concordance with the level of p53 expression.

• Journal of Life Science
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• v.25 no.12
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• pp.1377-1383
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• 2015

Scopoletin is a component of several plant such as Erycibe obtusifolia, Aster tataricus, Foeniculum vulgare and Brunfelsia grandiflora. It was reported to have anti-angiogenesis and anti-allergy effects. In this study, the anti-inflammatory effect of scopoletin was investigated in Raw264.7 cells, mouse macrophages. The effects of scopoletin on phagocytosis and nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced inflammatory responses. It was observed that scopoletin exerted inhibitory effects on both phagocytosis and NO production. In addition, scopoletin decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) which were related to NO and prostaglandin E2 (PGE2) production. In particular, the expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The expression levels of IL-1β, IL-6 were remarkably decreased by treatment with scopoletin. Furthermore, the content of TNFα produced by macrophage was decreased in the presence of scopoletin at 8 hr. These results indicate that the anti-inflammatory effect of scopoletin could exert by inhibiting the expression of pro-inflammatory cytokines in Raw264.7 cells stimulated with LPS. The above results suggest scopoletin could be a new remedial agent for anti-inflammation through inhibition of iNOS, COX-2, IL-1β, IL-6 and TNF-α expressions as well as supression of phagocytosis and NO production.

• Journal of Life Science
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• v.18 no.3
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• pp.329-335
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• 2008

Korean Deep ground sea-like water (KDSW) has a similar mineral composition with deep sea water. KDSW has demonstrated its usefulness and attracted in the medical fields. KDSW and Danasoo (desalted deep ground sea-like water) intake improve antioxidant, antidiabetic activity and immunity. Antioxidant activities of KDSW and Dnansoo were measured by using 2,2-diphenyl-l-picryl-hydrazyl (DPPH) free radical, superoxide dismutase-like activity (SODA) and photochemiluminescence (PCL). DPPH radical scavenging and SOD-like activities of KDSW and Danasoo were remarkably increased in a dose-dependent manner. Antioxidant activities of KDSW and Danasoo 85.32 and 14.02 nmol of ascorbic acid equivalent/ml KDSW and Danasoo, respectively, using the PCL method. Lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages RAW264.7 cells was inhibited up to 30% by treatment with Danasoo (20%). NO is synthesized by the enzyme of nitric oxide synthase (NOS) and plays an important role tumor growth and angiogenesis. The anticancer effects of Danasoo on human gastric and lung cancer cells was performed by levels of inducible nitric oxide synthase (iNOS). Danasoo significantly reduced iNOS expression of human gastric cancer (SNU-l) and lung carcinoma (A549). The serum glucose level was significantly reduced by Danasoo (20%) diet in streptozotocin (STZ)-induced diabetic rats. These result suggest that KDSW has excellent biological activities and thus it has great potential as a source for natural health products.

• Journal of Life Science
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• v.23 no.3
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• pp.462-469
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• 2013

Withaferin A is a steroidal lactone purified from the Indian medicinal plant Withania somnifera. It exhibits a wide variety of activities, including anti-tumor, anti-inflammation, and immunomodulation properties. In this review, we focused on the anti-cancer effects of withaferin A. Withaferin A inhibits cell proliferation, metastasis, invasion, and angiogenesis in cancer cells. Furthermore, it sensitized irradiation, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, and doxorubicin-mediated apoptosis. The results showed that multiple mechanisms were involved in withaferin A-mediated anti-cancer effects. First, withaferin A increased intracellular reactive oxygen species (ROS) production and induced ER stress- and mitochondria-mediated apoptosis. Second, withaferin A inhibited the signaling pathways (Jak/STAT, Akt, Notch, and c-Met), which are important in cell survival, proliferation, and metastasis. Third, it induced apoptosis and inhibited cancer cell migration through the up-regulation of prostate apoptosis protein-4 (Par-4). Finally, withaferin A up-regulated pro-apoptotic protein expression levels through the inhibition of proteasome activity. Our findings suggested that withaferin A is a potential, potent therapeutic agent.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.492-501
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• 1995

Background: Transforming growth factor- alpha(TGF-$\alpha$) may play important roles in carcinogenesis, tumor growth, and angiogenesis. Transforming growth factor-beta(TGF-$\beta$) are known to be involved in cell-cycle control and regeneration. TGF-$\alpha$ positively acts on growth control of many epithelial cells in contrast to the negative role of TGF-$\beta$. Method: To evaluate the possible role of TGF-$\alpha$ and TGF-$\beta$ in human primary lung cancers, the expression of TGF-$\alpha$ and TGF-$\beta$ were immmunohistochemically investigated in tissue sections from forty seven cases with lung cancers and ten cases with non-cancerous lung tissues. Recombinant cloned monoclonal antibody of TGF-$\alpha$ and neutralizing antibody of TGF-$\beta$ were employed as primary antibodies after dewaxing the formalin-fixed, paraffinized tissue sections. Results: TGF-$\alpha$ was expressed in the cytoplasms of tumor cells in thirty five cases of forty seven(74.5%) primary lung cancers, whereas the control expressed in two of ten brochial epithelial cells. The expression of TGF-$\alpha$ was disclosed in four cases of eleven(36.4 %) small cell carcinomas and thirty one cases of thirty six(86.1%) non-small cell carcinomas of the lung. Expressions of TGF-$\beta$ was discernible in bronchial epithelium in eight of ten non-cancerous lung tissues. The expression of TGF-$\beta$ was noted in the cytoplasms of tumor cells in eight cases of forty seven(17.0%) primary lung cancers. The expression of TGF-$\beta$ disclosed in two cases of eleven(18.2%) small cell carcinomas and six cases of thirty six(16.7%) non- small cell carcinomas of the lung. Conclusion: These findings suggest that up-regulation of TGF-$\alpha$ and down-regulation of TGF-$\beta$ are involved during development and growth of primary lung cancers.

• The Korean Journal of Malacology
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• v.30 no.2
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• pp.155-163
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• 2014

Serpins are a group of proteins involved in the regulation of serine and other type of proteases, and have been identified in many kinds of organisms from invertebrates to vertebrates. Serpins are known to regulate the proteolytic cascades of the innate immune pathways in addition to their roles in blood coagulation, angiogenesis, fibrinolysis, inflammation and tumor suppression. In this study, we have isolated two partial serpin gene fragments from expressed sequence tags (ESTs) of Nesiohelix samarangae. Dotplot analysis indicates that they are of two different types, Ns-serpin type 1 and Ns-serpin type 2. Ns-serpin type 1 has 819 bp coding region (272 amino acids), whereas Ns-serpin type 2 has 555 bp coding region (185 amino acids). Molecular phylogenetic analysis shows that the identified serpins have high similarities to their counterparts in the California see slug, Aplysia californica. Yet, the precise biological and immunological roles of these Ns-serpins remain to be further investigated using RNA interference and other molecular techniques.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.155-161
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• 2001

Background and Objectives: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. This reaction is catalyzed by nitric oxide synthase (NOS). NO is an important bioactive agent and a signalling molecule that mediates a variety of biologic actions such as vasodilation, neurotransmission, host defense, and iron metabolism but increased NO production may also contribute to the pathogenesis of a various of disorders, including cancer. Before now, the role of NO in thyroid gland is still investigated and it was supposed that NO mediate the angiogenesis in tumor growth. Others journal and works identified the expression of iNOS that involve by neutrophil and eNOS that involve in part in the vascular remodeling and to understand the role of NO in human thyroid gland. But authors revealed only eNOS in thyroid neoplasm. iNOS was identifed by inflammation in fault. Materials and Methods: Western blot analysis was performed, using a polyclonal antibody against eNOS (Rabbit polyclonal IgG). Using the same antibody, the distribution of eNOS was examined in 15 formalin-fixed paraffin embedded samples by immunohistochemistry. By NADPH consumption rate, NOS activity was estimated at nodular hyperplasia. Results: Western blot analysis exhibited that eNOS was significantly elevated in thyroid papillary carcinoma, compared to that in nodular hyperplasia and normal tissue. Immunohistochemistry showed that the immunoreacitivity was present more significantly in thyroid follicular epithelial cell layer than vascular endothelial cell. NOS activity increased in nodular hyperplasia. Conclusions: Thyroid papillary cancer without neutrophil invasion expressed only eNOS. The endothelial localization of eNOS may play an important role in pathogenensis of human thyroid nodular hyperplasia and the follicular localization of thyroid papillary carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1457-1461
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• 2012

Purpose: Non small cell lung cancer (NSCLC) is the leading worldwide source of cancer-related deaths. Although some drugs targeting EGFR mutations have been developed, most advanced cases are still incurable. New targets for anticancer drugs are demanded. The kringle 1 domain of hepatocellular growth factor alpha chain (HGFK1) is a potent anti-angiogenesis factor. It has also emerged as a potential anticancer factor in hepatocellular carcinoma (HCC). The expression of HGFK1 protein in patients with NSCLC has not been reported to date. Method: Here, we assessed HGFK1 expression by Western blotting in 103 cases with advanced NSCLC to investigate the impact of HGFK1 on survival. Results: Results revealed 33 (30.1%) patients were classified as high expressors, this being significantly associated with less remote metastasis (P = 0.002) but not with lymph node metastasis (P = 0.062). There was also a significant association between HGFK1 expression and tumor size (P = 0.025) as well as clinical stage (P = 0.012). Kaplan-Meier survival analysis showed that both overall survival (OS) and progression free survival (PFS) of patients with HGFK1 expression were longer than those of patients without HGFK1 expression (P = 0.004 and P = 0.001 respectively). HGFK1 reversed gefitinib inhibition in the resistent NSCLC cell line A431/GR but did not inhibit the proliferation of NSCLC cells A431 and A431/GR directly. Reversion of gefitinib inhibition in A431/GR cells by HGFK1 was related to decreased phosphorylation of ERK and STAT5. Conclusions: HGFK1 may be a useful prognostic factor of advanced NSCLC patients and a potential drug for gefitinib resistant patients.

• Journal of Life Science
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• v.14 no.1
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• pp.154-162
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• 2004

Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated and at transcriptional level by external stimuli. Previously, we found that phorbol 12-myristate 13-acetate (PMA) suppressed TSP-1 expression in porcine aortic endothelial (PAE) cell, but enhanced in hepatoma cell line, Hep 3B cell. A region between -767 and -723 on the tsp-1 promoter was defined as a responsive site to the suppression in PAE cell. eased on the previous results, the molecular mechanism of TSP-1 expression was determined by characterizing interactions between cis-elements and trans-factors using three overlapped oligonucleotide probes, oligo a-1 (from -767 to -738), a-2 (-759 to -730) and a-3 (-752 to -723). The results from electromobility shift assay showed that PMA-induced suppression of TSP-1 transcription in PAE cell might be caused via a negative regulator binding to the region from -752 to -730 and additionally generated by lacking two positive regulators binding to the sites from -767 to -760 and from -752 to -730. Especially, PMA enhanced the binding ability of the negative regulator to the site from -752 to -730 in PAE cell, but anti-c-Jun did not affected its binding ability.