• 대한한방종양학회지
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• 제5권1호
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• pp.19-32
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• 1999

To evaluate the antitumor activity and antimetastatic effects of Kamigumgusingihwan(KGSH) studies have ken done. The results were obtained as follows: 1. KGSH extracts exhibited a weak cytotoxicity against A549, SK-OV-3, B16-F10, and SK-MEL-2 cell lines. But exhibited potent cytotoxicity against P388 cell line in a dose-dependent manner. 2. The concentration inhibiting adhesion of A549, to complex extracellular matrix up to below 30% of control was recognized at $10^{-3}g/ml$ of KGSH 3. KGSH extracts showed a weak inhibitoty effect on DNA topo-isomerase I from calf thymus. 4. The T/C% was 137% in KGSH treated group in S-180 bearing ICR mice. 5. In pulmonary colonization assay, a number of colonies in the lungs were decreased significantly in KGSH treated group as compared with control group. 6. In hematological changes in B16-BL6 injected C57BL/6, numbers of WBC were decreased insignificantly in KGSH treated groups, and also those of platelet were increased insignificantly in KGSH treated groups as compared with control. 7. In CAM assay, KGSH extracts inhibited angiogenesis at $15{\mu}g/egg $concentration significantly as compared with control. Taken together these results, it is strongly demonstrated that KGSH significantly suppressed tumor metastasis by blocking cell adhesion to extracellular matrix. Therefore, KGSH is expected to be clinically a potent antimetastatic drug for the prevention and treatment of cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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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.

• International Journal of Oral Biology
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• 제45권4호
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• pp.218-224
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• 2020

The antitumor effects of octyl gallate (OG) were investigated on FaDu human hypopharyngeal squamous carcinoma cells. At various concentrations, OG inhibited the proliferation of FaDu cells by suppressing cell cycle regulators and induced apoptosis by activating caspase 3 and its downstream poly (ADP-ribose) polymerase, thereby damaging DNA. Immunoblotting demonstrated that OG significantly suppressed the expression of integrin family proteins (integrin α4, αv, β3, β4), hindering cell adhesion. The reduced expression of integrins subsequently mediated the mitogen-activated protein kinase signaling pathway to stimulate the activation of extracellular signal-regulated kinases and c-jun N-terminal kinases, leading to apoptosis. Thus, OG demonstrated antitumor activity on hypopharyngeal squamous carcinoma cells by suppressing cell proliferation and inducing apoptosis.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.59-64
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• 2011

Dimeric sesquiterpenoid shizukaol B (SKB) was isolated from Chloranthus japonicus Sieb. Except that SKB inhibited adhesion molecule expression in monocytes and endothelial cells, no more biological and pharmacological activity of SKB had been reported until now. In this study, we examined immunosuppressive activity of SKB. SKB strongly inhibited lipopolysaccharide (LPS)-induced B cell proliferation with $IC_{50}$ of 137 ng/ml, but slightly or not concanavalin A-induced T cell proliferation, LPS-induced macrophage NO production, and LPS-induced dendritic cell maturation. As a mechanism, SKB strongly induced apoptotic death of B cells, but not other cell types. These results suggested that SKB induced toxicity-mediated immunosuppression against B cells.

• 혜화의학회지
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• 제10권2호
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• pp.21-29
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• 2002

To evaluate the antitumor activity and antimetastatic effects of Polygoni Orientalis Fructus(POF), studies were done experimentally. The results were obtained as follows : 1. In cytotoxicity against A549, and XF498 cell concentration inhibiting cell growth up to below 30% of control was recognized at $200{\mu}g/m{\ell}$ of POF. Also POF inhibited cell growth up to below 30% of control against SK-OV-3, SK-MEL-2, HCT15 and MCF-7 cell at $100{\mu}g/m{\ell}$. 2. The concentration inhibiting adhesion of A549 and SK-OV-3 to complex extracellular matrix up to below 70% of control was recognized at $100{\mu}g/m{\ell}$ of POF. 3. In pumonary colonization assay, a number of colonies in the lungs were decreased significantly in POF treated group as compared with control group. These results suggested that POF extracts might be usefully applied for prevention and treatment of cancer.

• 생명과학회지
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• 제18권1호
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• pp.75-83
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• 2008

인체 DNA topoisomerase는 DNA를 단일 또는 두 가닥을 일시적인 절단을 촉매하여 DNA의 topological 문제를 조절함으로써, DNA 복제, 전사, 재조합과 유사분열 과정 등에 관여한다. 이 효소는 많은 항생, 항암제의 표적효소로서 널리 알려져 있으며, 이들 유도체를 이용한 다양한 억제제의 개발과 임상적 응용에 관한 연구가 활발하게 진행되고 있다. 본 실험에서는 인체 백혈병 HL-60 세포에서 topoisomerase 억제제가 topoisomerase 기능 활성과 유전자 발현을 조절하는지를 규명하기 위하여 본 연구를 수행하였다. 연구 방법은 HL-60세포에 topoisomerase type I과 type II의 대표적 억제제인 10-hydroxycamptothecin (10-CPT)과 doxorubicin을 투여한 후 total RNA를 분리하였고, 10K-oligo-nucleotide microarray 방법으로 분석하여 유전자의 발현 양상을 조사하였다. 연구 결과에 의하면 10-CPT 또는 doxorubicin을 투여한 HL-60세포에서의 유전자 발현 양상은 주로 signal transduction, cell adhesion, cell cycle, cell growth, cell proliferation, cell differentiation, transcription 및 immune response 등과 관련이 있었다. Topoisomerase type I의 억제제인 10-CPT를 HL-60 세포주에 투여 하였을 때 type I으로 분류되는 topoisomerase III${\alpha}$, III${\beta}$ 및 I의 발현은 증가하였으나 type II인 topoisomerase II${\alpha}$와 II${\beta}$의 유전자의 발현은 감소되었다. 반대로 type II의 억제제인 doxorubicin을 투여하였을 때는 앞의 결과와 상반된 topoisomerase II${\alpha}$와 II${\beta}$의 유전자의 발현이 현저히 증가되었으며, topoisomerase III${\alpha}$와 III${\beta}$의 mRNA의 발현은 약간 감소하는 양상을 보였으나 의미 있는 차이는 없었다. 이 연구 결과는 앞으로 항암제의 기전을 밝히고 약물에 대한 치료 반응을 예측하고 새로운 약제 개발에 기초자료가 될 것으로 여겨진다.

• Nutrition Research and Practice
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• 제14권2호
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• pp.127-133
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• 2020

BACKGROUND/OBJECTIVES: Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells. MATERIALS/METHODS: Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action. RESULTS: Administration with up to 40 μM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 μM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels. CONCLUSIONS: Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

• 대한한의학회지
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• 제22권2호
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• pp.22-30
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• 2001

This study was attempted to investigate the anti-tumor and anti-metastatic effects of Sobokchukeotang(SBCT) and Kamisobokchukeotang(KSBCT). Cytotoxicity against various cancer cell lines, anti-adhesion, pulmonary colonization, anti-angiogenesis, and T/C% were evaluated. SBCT and KSBCT exhibited no cytotoxicity against HT-1080, A549, SK-OV-3, B16-F10 and SK-Mel-2 cell lines. In inhibitory effect on DNA topoisomerase I, the $IC_{50S}$ were shown $250-500{\;}\mu\textrm{g}/ml$ of SBCT and $62.5-125{\;}\mu\textrm{g}/ml$ of KSBCT respectively. In the in vivo experiments, SBCT(135.98%) and KSBCT(151.92%) apparently increased the life span of mice bearing sarcoma-180. KSBCT significantly inhibited the adhesion of HT-1080 to complex extracellular matrix in a dose-dependent manner in contrast to SBCT. In pulmonary colonization assay by B16-F10, a number of colonies in the lungs were decreased more significantly in KSBCT group than those in SBCT group. In vitro neovascularization and CAM assay, angiogenesis was more significantly inhibited in KSBCT-treated group than in SBCT- treated group. Above results suggests that KSBCT is more effectively applied to prevention and treatment of cancer than SBCT.

• 한국식품영양과학회지
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• 제43권7호
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• pp.1009-1016
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• 2014

묵은지 스타터로 개발된 Lb. curvatus ML17의 생균제적 특성 및 기능성 조사를 통하여 기능성 소재로서의 개발 가능성을 검토하였다. Lb. curvatus ML17은 용혈현상을 일으키지 않았으며 ${\beta}$-glucosidase와 ${\beta}$-glucuronidase의 발암효소 활성이 없는 것으로 나타나 균주에 대한 안전성을 확인하였다. 장내 생존성 확인 실험에서는 인공위액에서 2시간 처리한 다음 인공담즙에서 24시간 처리한 결과 초기 균수 대비 12.30%의 생존율을 나타내었다. Caco-2 cell에 대한 부착율은 초기 접종균수가 많을수록 높게 나타났으며, $5.66{\times}10^9$ CFU/mL로 처리 시 17.31%의 부착율을 나타냈는데 20.78%의 부착율을 나타낸 양성 대조군 Lb. rhamnosus GG에 근접하게 높은 부착율을 나타내어 장내환경에서 바람직한 작용을 할 수 있음을 보여주었다. 유해균주에 대한 생육저해 활성 측정에서는 Micrococcus luteus, Bacillus cereus, Salmonella enterica subsp. enterica, Pseudomonas aeruginosa에 대하여 우수한 항균 활성을 나타내었다. DPPH radical 소거능을 이용한 항산화 활성 측정 결과 72.88%로 양성 대조군인 0.1 mg/mL ascorbic acid보다 높은 free radical 소거능을 나타내었다. AGS 위암세포 및 HT-29 결장암세포에 대한 성장 억제 효과에서는 Lb. curvatus ML17의 배양 상등액 $80{\mu}L/mL$ 처리 시 각각 82.91% 및 79.35%의 암세포 성장 억제 효과를 나타내었다. 이와 같은 결과로 Lb. curvatus ML17이 묵은지를 포함한 발효스타터로 사용되었을 경우 식품의 보존성 향상과 품질 유지 및 균주에 의한 건강 기능성을 부여할 수 있으며 식품, 사료, 의약 분야의 다양한 산업적 활용이 기대된다.

• Journal of Periodontal and Implant Science
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• 제42권6호
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• pp.248-255
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• 2012

Purpose: The aim of the present study was to evaluate the biological response of alkali- and heat-treated titanium-8tantalum-3niobium surfaces by cell proliferation and alkaline phosphatase (ALP) activity analysis. Methods: Commercial pure titanium (group cp-Ti) and alkali- and heat-treated titanium-8tantalum-3niobium (group AHT) disks were prepared. The surface properties were evaluated using scanning electron microscopy, energy dispersed spectroscopy and X-ray photoelectron spectroscopy (XPS). The surface roughness was evaluated by atomic force microscopy and a profilometer. The contact angle and surface energy were also analyzed. The biological response of fetal rat calvarial cells on group AHT was assessed by cell proliferation and ALP activity. Results: Group AHT showed a flake-like morphology microprofile and dense structure. XPS analysis of group AHT showed an increased amount of oxygen in the basic hydroxyl residue of titanium hydroxide groups compared with group cp-Ti. The surface roughness (Ra) measured by a profilometer showed no significant difference (P>0.05). Group AHT showed a lower contact angle and higher surface energy than group cp-Ti. Cell proliferation on group AHT surfaces was significantly higher than on group cp-Ti surfaces (P<0.05). In comparison to group cp-Ti, group AHT enhanced ALP activity (P<0.05). Conclusions: These results suggest that group AHT stimulates osteoblast differentiation.