• BMB Reports
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• 제51권9호
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• pp.425-426
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• 2018

As highly conserved signaling cascades of multicellular organisms, Wnt and Hippo pathways control a wide range of cellular activities, including cell adhesion, fate determination, cell cycle, motility, polarity, and metabolism. Dysregulation of those pathways are implicated in many human diseases, including cancer. Similarly to ${\beta}-catenin$ in the Wnt pathway, the YAP transcription co-activator is a major player in Hippo. Although the intracellular dynamics of YAP are well-known to largely depend on phosphorylation by LATS and AMPK kinases, the molecular effector of YAP cytosolic translocation remains unidentified. Recently, we reported that the Dishevelled (DVL), a key scaffolding protein between canonical and non-canonical Wnt pathway, is responsible for nuclear export of phosphorylated YAP. The DVL is also required for YAP intracellular trafficking induced by E-cadherin, ${\alpha}-catenin$, or metabolic stress. Note that the p53/LATS2 and LKB1/AMPK tumor suppressor axes, commonly inactivated in human cancer, govern the reciprocal inhibition between DVL and YAP. Conversely, loss of the tumor suppressor allows co-activation of YAP and Wnt independent of epithelial polarity or contact inhibition in human cancer. These observations provide novel mechanistic insight into (1) a tight molecular connection merging the Wnt and Hippo pathways, and (2) the importance of tumor suppressor contexts with respect to controlled proliferation and epithelial polarity regulated by cell adhesion.

• 동의생리병리학회지
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• 제34권3호
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• pp.126-135
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• 2020

The purpose of this study was to investigate the antioxidant, anti-inflammatory and anti-cellular adhesion molecules effects of Allii Macrostemonis Bulbus, Artemisiae Capillaris Herba, Curcumae Radix, Crataegi Fructus, Salviae Militiorrhizae Radix complex extract(AMCP) on the inhibition of atherosclerosis in HUVEC. We measured DPPH radical scavenging activity and ABTS radical scavenging activity of AMCP to evaluate its antioxidant effect. And we also measured the expression level of NF-κB, IκBα, ERK, JNK, p38 proteins to evaluate its anti-inflammatory effect. Lastly, we measured the expression level of MCP-1, ICAM-1, VCAM-1 mRNA and their level to evaluate its anti-celluar adhesion molecules. AMCP did not show any cytotoxicity in HUVEC within the concentraion tested except for a concentration of 400 ㎍/㎖. AMCP increased the DPPH radical scavenging activitiy and ABTS radical scavenging activity in HUVEC as the concentration of AMCP rises. AMCP significantly reduced NF-κB, IκBα, JNK, ERK and p38 protein expression in HUVEC compared to control group. AMCP significantly reduced MCP-1, ICAM-1, VCAM-1 gene expresion in HUVEC compared to control group. AMCP significantly decreased the levels of MCP-1, ICAM-1, VCAM-1 in HUVEC compared to control group. These results suggest that AMCP has effects on antioxidation, anti-inflammation and anti-cellular adhesion molecule, which helps the treatment and prevention of dyslipidemia and atherosclerosis.

• International Journal of Oral Biology
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• 제37권4호
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• pp.189-195
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• 2012

Resistance to the induction of apoptosis is a possible mechanism by which tumor cells can survive anti-neoplastic treatments. Melanoma is notoriously resistant to anti-neoplastic therapy. Previous studies have demonstrated focal adhesion kinase (FAK) overexpression in melanoma cell lines. Given its probable role in mediating resistance to apoptosis, many researchers have sought to determine whether the downregulation of FAK in melanoma cells would confer a greater sensitivity to anti-neoplastic agents. Genistein is a known inhibitor of protein-tyrosine kinase (PTK), which may attenuate the growth of cancer cells by inhibiting the PTK-mediated signaling pathway. This present study was undertaken to investigate the effect of genistein on the expression of FAK and cell cycle related proteins in the G361 melanoma cell line. Genistein was found to have a preferential cytotoxic effect on G361 melanoma cells over HaCaT normal keratinocytes. Genistein decreased the expression of 125 kDa phosphotyrosine kinase and the FAK protein in particular. Genistein treatment did not affect the expression of p53 in G361 cells in which p21 is upregulated. The expression of cyclin B and cdc2 was downregulated by genistein treatment. Taken together, our data indicate that genistein induces the decreased proliferation of G361 melanoma cells via the inhibition of FAK expression and regulation of cell cycle genes. This suggests that the use of genistein may be a viable approach to future melanoma treatments.

• Fisheries and Aquatic Sciences
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• 제22권3호
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• pp.7.1-7.10
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• 2019

Sargassum serratifolium ethanolic extract has been known for strong antioxidant and anti-inflammatory properties. We prepared hexane fraction from the ethanolic extract of S. serratifolium (HSS) to improve biological activities. In this study, we investigated the effects of HSS on the inhibition of tumor necrosis factor (TNF)-${\alpha}$-induced monocyte adhesion to human umbilical vein endothelial cells (HUVECs). We found that HSS suppressed the production of cell adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in TNF-${\alpha}$-induced HUVECs. Moreover, TNF-${\alpha}$-induced production of monocyte chemoattractant protein 1 and keratinocyte chemoattractant was inhibited by HSS treatment. HSS suppressed TNF-${\alpha}$-induced nuclear factor kappa B ($NF-{\kappa}B$) activation via preventing proteolytic degradation of inhibitor ${\kappa}B-{\alpha}$. HSS induced the production of heme oxygenase 1 via translocation of Nrf2 into the nucleus in TNF-${\alpha}$-treated HUVECs. Overall, HSS alleviated vascular inflammation through the downregulation of $NF-{\kappa}B$ activation and the upregulation of Nrf2 activation in TNF-${\alpha}$-induced HUVECs. These results indicate that HSS may be used as therapeutic agents for vascular inflammatory disorders.

• 한국해양바이오학회지
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• 제1권3호
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• pp.156-162
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.

• Molecules and Cells
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• 제25권2호
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• pp.184-195
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• 2008

We examined the role of c-FLIP in the motility of HeLa cells. A small interfering RNA (siRNA) directed against c-FLIP inhibited the adhesion and motility of the cells without affecting their growth rate. The long form of c-FLIP ($c-FLIP_L$), but not the short form ($c-FLIP_S$), enhanced adhesion and motility. Downregulation of $c-FLIP_L$ with siRNA decreased phosphorylation of FAK and ERK, while overexpression of $c-FLIP_L$ increased their phosphorylation. Overexpression of FAK activated ERK, and enhanced the motility of HeLa cells. FRNK, an inhibitory fragment of FAK, inhibited ERK and decreased motility. Inhibition of ERK also significantly suppressed $c-FLIP_L$-promoted motility. Inhibition of ROCK by Y27632 suppressed the $c-FLIP_L$-promoted motility by reducing phosphorylation of FAK and ERK. Overexpression of $c-FLIP_L$ increased the expression and secretion of MMP-9, and inhibition of MMP-9 by Ilomastat reduced $c-FLIP_L$- promoted cell motility. A caspase-like domain (amino acids 222-376) was found to be necessary for the $c-FLIP_L$-promoted cell motility. We conclude that $c-FLIP_L$ promotes the motility of HeLa cells by activating FAK and ERK, and increasing MMP-9 expression.

• 동의생리병리학회지
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• 제19권2호
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• pp.370-374
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• 2005

Streptococcus mutans (S. mutans) is known as the causative bacterial playing the most important role informing plaque and it is being noticed as major causative bacteria of dental caries. Therefore, development of more effective, substantial and safe preventive agent against dental caries and periodontal disease is honestly required. The present study was designed to investigate the effect of Cyperus rotundus (Cyperaceae) methanol extracts on the growth, acid production, adhesion, and insoluble glucan synthesis of S. mutans. The methanol extract of C. rotundus showed concentration dependent inhibitory activity against the growth and acid production of S. mutans, and produced significant inhibition at the concentration of 0.5, 1, 2 and 4 mg/ml compared to the control group. The extracts markedly inhibited S. mutans adherence to HA treated with saliva, and cell adherence was repressed by more than 50% at the concentration of 0.5 mg/ml and complete inhibition was observed at the concentration of 4 mg/ml. On the activity of glucosyltransferase which synthesizes water insoluble glucan from sucrose, methanol extract of C. rotundus showed more than 10% inhibition over the concentration of 2 mg/ml. Thus, the application of C. rotundus can be considered a useful and a practical method for the prevention of dental caries.

• The Korean Journal of Physiology and Pharmacology
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• 제1권1호
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• pp.71-78
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• 1997

In an attempt to investigate the role of phospholipase $A_2$($PLA_2$) in interleukin-l (IL-l) induced acute lung injury, mepacrine was tried to inhibit $PLA_2$ in IL-l induced ARDS rats. For confirmation of acute lung injury by IL-l, and to know the role of neutrophils in this injury, lung leak index, lung myeloperoxidase(MPO), number of neutrophils and protein content in the bronchoalveolar lavage (BAL) and wet lung weight were measured. At the same time lung $PLA_2$ was measured to know the effect of IL-l on $PLA_2$ activity. Pulmonary surfactant was also measured for an investigation of type II alveolar cell function. Neutrophil adhesion assay was performed to know the effect of $PLA_2$ inhibition in vitro with human umbilical vein endothelial cells (HUVEC). For precise location of injury by IL-l, morpholgical study was performed by electron microscopy. Five hours after instillation of IL-l (50 ng/rat), lung leak index, protein content, number of neutrophils, lung MPO and wet lung weight were increased significantly. Five hours after IL-l instillation lung $PLA_2$ activity was increased significantly, and increased surfactant release was observed in IL-l induced ARDS rats' BAL. In contrast, in rats given mepacrine and IL-l, there was decrease of acute lung injury i.e. decrease of lung leak index, wet lung weight, protein content, number of neutrophils in BAL and decreased lung MPO activity. Mepacrine decreased surfactant release also. Interestingly, inhibition of $PLA_2$ decreased adhesion of human neutrophils to HUVEC in vitro. Morphologically, IL-l caused diffuse necrosis of endothelial cells, type I and II epithelial cells and increased the infiltration of neutrophils in the interstitium of the lung but after mepacrine treatment these pathological findings were lessened. On the basis of these experimental results it is suggested that $PLA_2$ has a major role in the pathogenesis of acute lung injury mediated by neutrophil dependent manner in IL-l induced acute lung injury.

• 환경생물
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• 제27권1호
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• pp.88-94
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• 2009

안토시아닌(Anthocyanin)은 플라보노이드계 화합물의 한 부류로 항산화, 항암 및 항궤양, 항당뇨, 중금속해독, 시력보호, 콜레스테를 저하 등의 다양한 생리활성을 가지는 것으로 보고되어 있다. 죽상경화과정은 염증성 사이토카인의 분비 또는 혈관손상으로 인한 백혈구의 부착과 이동을 통해 시작된다. 본 연구는 이러한 죽상경화의 초기과정에서 안토시아닌 혼합물 중 single compound인 delphinidin chloride (DC) 인간혈관 내피세포주(HUVEC, human umbilical vein endothelial cell line)에서 백혈구 부착과 관련이 있는 ICAM-1 (Intraceliular Adhesion Molecule-1)과 VCAM-1 (Vascular Adhesion Molecule-1) 발현에 미치는 영향에 대해 조사하였다. 세포독성이 없는 농도에서 TNF-$\alpha$에 의해 유도된 혈관 내피세포에 대한 단핵구의 부착정도를 측정하기 위해 monocyte-endothelial cell adhesion assay와 광학현미경을 이용한 형태학적 관찰을 한 결과 DC가 처리농도 의존적으로 부착을 억제하였다. 내피세포로부터 TNF-$\alpha$에 의해 유도된 세포부착 분자인 VCAM-1과 ICAM-1의 발현에 대한 영향을 western blot analysis 및 RT-PCR방법으로 비교 분석한 결과 VCAM-1과 ICAM-1의 단백질과 mRNA수준에서의 발현이 농도 의존적으로 감소되었다. 이러한 결과들을 종합해 볼 때 안토시아닌 중에서 DC를 실험한 결과 DE는 TNF-$\alpha$에 의해 유도된 내피세포의 ICAM-1과 VCAM-1 발현 억제효과를 확인할 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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• pp.133-137
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• 2013

Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-${\kappa}B$) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaB${\alpha}$ ($I{\kappa}B{\alpha}$) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of $I{\kappa}B{\alpha}$ expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.