• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1791-1795
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• 2013

Aims and Background: Prostate cancer is one of the most common malignant tumors in the male reproductive system, which causes the second most cancer deaths of males, and control of angiogenesis in prostate lesions is of obvious importance. This study assessed the effect of apogossypolone (ApoG2) on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs). Subjects and Methods: HUVECs were treated with different concentrations of ApoG2. The survival rate of HUVECs were determined by MTT assay. Utrastructural changes of HUVECs were assessed with transmission electron microscopy. Apoptosis in HUVECs was analyzed by flow cytometry and cell migration by Boyden chamber assay. Matrigel assays were used to quantify the development of tube-like networks. Results: ApoG2 significantly inhibited HUVEC growth even at 24 h (P<0.05). The inhibitory effect of ApoG2 is more obvious as the concentration and the culture time increased (P<0.05). These results indicate that ApoG2 inhibits the proliferation of HUVECs in a time- and concentration-dependent manner with increase of the apoptosis rate. Besides, ApoG2 reduced the formation of total pseudotubule length and network branches of HUVECs. Conclusions: The results suggest that ApoG2 inhibits angiogenesis of HUVECs by growth inhibition and apoptosis induction.

• Fisheries and Aquatic Sciences
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• v.22 no.3
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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.

• The Journal of Korean Society for Radiation Therapy
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• v.14 no.1
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• pp.165-174
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• 2002

Vascular endothelial growth factor (VEGF) has been identified as a peptide growth factor specific for vascular endothelial cells. In this study, we examined the effect of VEGF on radiation induced apoptosis and receptor/second messenger signal transduction pathway for VEGF effect in human umbilical vein endothelial cells (HUVECs). VEGF was found to protect HUVECs against the lethal effects of ionizing radiation by inhibiting the apoptosis induced in these cells by radiation exposure. VEGF (1-30 ng/ml) dose dependently inhibited apoptosis by irradiation. Pre-treatment with Flt-1 and Flk-l/KDR receptor blocked the VEGF-in duced antiapoptotic effect. Phosphatidylinositol 3'-kinase (PI3-kinase) specific inhibitor, Wortman in and LY294002, blocked the VEGF-induced antiapoptotic effect. These data suggest that VEGF may play an important role in survival of HUVECs due to the prevention of apoptotic cell death caused by some stresses such as ionizing radiation.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.425-437
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• 2021

Although the contributions of sitagliptin to endothelial dysfunction in diabetes mellitus were previously reported, the mechanisms still undefined. Autophagy plays an important role in the development of diabetes mellitus, but its role in diabetic macrovascular complications is unclear. This study aims to observe the effect of sitagliptin on macrovascular endothelium in diabetes and explore the role of autophagy in this process. Diabetic rats were induced through administration of high-fat diet and intraperitoneal injection of streptozotocin. Then diabetic rats were treated with or without sitagliptin for 12 weeks. Endothelial damage and autophagy were measured. Human umbilical vein endothelial cells were cultured either in normal glucose or in high glucose medium and intervened with different concentrations of sitagliptin. Rapamycin was used to induce autophagy. Cell viability, apoptosis and autophagy were detected. The expressions of proteins in c-Jun N-terminal kinase (JNK)-Bcl-2-Beclin-1 pathway were measured. Sitagliptin attenuated injuries of endothelium in vivo and in vitro. The expression of microtubuleassociated protein 1 light chain 3 II (LC3II) and beclin-1 were increased in aortas of diabetic rats and cells cultured with high-glucose, while sitagliptin inhibited the over-expression of LC3II and beclin-1. In vitro pre-treatment with sitagliptin decreased rapamycin-induced autophagy. However, after pretreatment with rapamycin, the protective effect of sitagliptin on endothelial cells was abolished. Further studies revealed sitagliptin increased the expression of Bcl-2, while inhibited the expression of JNK in vivo. Sitagliptin attenuates injuries of vascular endothelial cells caused by high glucose through inhibiting over-activated autophagy. JNK-Bcl-2-Beclin-1 pathway may be involved in this process.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.445-450
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• 2011

In order to validate the use of Olibanum as an anti-inflammatory drug in the traditional Korean medicine, I have investigated the effect of water-soluble extract of Olibanum (EO) on the expression of pro-inflammatory vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-${\alpha}$. The extract inhibited dose-dependently VCAM-1 expression without its cytotoxic effect on HUVECs, as measured by a flow cytometer using fluorescence-enhanced anti-VCAM-1 antibody, and significantly decreased mRNA levels of VCAM-1, as determined using reverse transcription polymerase chain reaction. These results suggest that Olibanum may have therapeutic potential in the control of endothelial disorders caused by inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.5
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• pp.175-180
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• 2022

The seeds of Trichosanthes kirilowii (STK) used in traditional Oriental medicine for the treatment of dry cough and constipation have diverse pharmacological activities, including hypolipidemic, antioxidant, immunosuppressive, and anticancer effects. However, the effect of STK on angiogenesis has not been studied yet. In this study, we investigated whether the ethanolic extract of STK (ESTK) can regulate the migration and tube formation of human umbilical vein endothelial cells (HUVECs) and explored the underlying mechanism. Results of transwell assay showed that ESTK treatment dose-dependently suppressed the migration of HUVECs. The conditioned medium collected from H1299 human lung cancer cells was used as a chemoattractant. Our observation suggests that ESTK would inhibit the recruitment of endothelial cells into tumors. In addition, ESTK treatment significantly reduced the tube formation of HUVECs. As a molecular mechanism, we found that vascular endothelial growth factor (VEGF)-induced phosphorylation of VEGF receptor 2 (VEGFR2) was completely blocked by ESTK treatment. The expression of angiogenic factors, including VEGFA, fibroblast growth factor 2 (FGF2), angiopoietin, placental growth factor (PGF), platelet derived growth factor (PDGF), angiogenin, and tumor necrosis factor (TNF)-α, was commonly decreased by ESTK treatment in H1299 cells, indicating that ESTK would reduce the production of angiogenic factors from cancer cells. Taken together, our results clearly demonstrated that ESTK exhibited anti-angiogenic effects in HUVECs, which provides another possible mechanism underlying the anticancer activities of STK.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.4
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• pp.872-882
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• 2009

Sachil-Tang (SCT) has been traditionally used as a prescription of spasm of the esophagus by stress, pectoralgia and oppressive feeling of the chest in Oriental medicine. This study was carried out to investigate the antioxidant activities of the ethanol extract of SCT and its inhibitory effect on intracellular oxidation and vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells (HUVECs) using various methods. The SCT extract showed a strong inhibitory effect on free radical generating model systems, including DPPH radical, superoxide anions, hydroxyl radical, peroxynirite and nitric oxide. Besides, the SCT extract exhibited a strong inhibitory effect on lipid peroxidation in rat liver homogenate induced by $FeCl_2$-ascorbic acid, and protected plasmid DNA against the strand breakage in a Fenton's reaction system. The SCT extract also inhibited copper-mediated oxidation of human low-density lipoprotein (LDL), and repressed relative electrophoretic mobility of LDL. Furthermore, the SCT extract protected intracellular oxidation induced by various free radical generators and inhibited expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. These results suggest that SCT can be an effective natural antioxidant and a possible medicine of atherosclerosis.

• Journal of Life Science
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• v.23 no.7
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• pp.926-932
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• 2013

Glutamine and serum are essential for cell survival and proliferation in vitro, yet the signaling pathways that sense glutamine and serum levels in endothelial cells remain uninvestigated. In this study, we examined the effects of glutamine deprivation and serum starvation on the fate of endothelial cells using a human umbilical vein endothelial cell (HUVEC) model. Our data indicated that glutamine deprivation and serum starvation trigger a progressive reduction in cell viability through apoptosis induction in HUVECs as determined by DAPI staining and flow cytometry analysis. Although the apoptotic effects were more predominant in the glutamine deprivation condition, both apoptotic actions were associated with an increase in the Bax/Bcl-2 (or Bcl-xL) ratio, down-regulation of the inhibitor of apoptosis protein (IAP) family proteins, activation of caspase activities, and concomitant degradation of poly (ADP-ribose) polymerases. Moreover, down-regulation of the expression of Bid or up-regulation of truncated Bid (tBid) were observed in cells grown under the same conditions, indicating that glutamine deprivation and serum starvation induce the apoptosis of HUVECs through a signaling cascade involving death-receptor-mediated extrinsic pathways, as well as mitochondria-mediated intrinsic caspase pathways. However, apoptosis was not induced in cells grown in glutamine- and serum-free media when compared with cells exposed to glutamine deprivation or serum starvation alone. Taken together, our data indicate that glutamine deprivation and serum starvation suppress cell viability without apoptosis induction in HUVECs.

• IMMUNE NETWORK
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• v.8 no.3
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• pp.75-81
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• 2008

Background: Platelets take part in repairing the lesions of endothelial damage. To understand the molecular mechanism of this process, we tested the hypothesis that CD154 expressed on activated platelets stimulates proliferation of human endothelial cells. Methods: The expression levels of CD154 and CD40 on platelets and endothelial cells, respectively, were measured by flow cytometry and confocal microscopy. Function-blocking monoclonal antibody against CD154 was developed after immunization with CD154-transfected L cells. Results: An anti-CD40 agonist antibody and soluble CD154 both induced significant proliferation of endothelial cells. In addition, a function-blocking anti-CD154 antibody inhibited the platelet-induced proliferation of endothelial cells, indicating that the CD154-CD40 pathway is involved in these cellular interactions. An anti-VEGF antibody failed to inhibit the proliferation. This, in addition to the fact that very small amounts of VEGF are released from platelets or endothelial cells, suggests that VEGF does not play an important role in the platelet-stimulated proliferation of endothelial cells. Conclusion: Our results indicate that platelets induce proliferation of endothelial cells by CD154-CD40 interactions independently of VEGF.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.246-254
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• 2023

Background: Here, we aimed to assess the inhibitory effect of a new compound from Panax ginseng on the migration of human ovarian cancer cells and tube formation of human umbilical vein endothelial cells (HUVECs). Methods: A new compound, ginsenglactone A (1), was isolated from ginseng roots, together with seven known compounds (2-8). Spectroscopic data were used to elucidate the chemical structure of 1. The tubular structure formation in HUVECs was assessed by Mayer's hematoxylin staining. The migration of A2780 cells was evaluated using the scratch wound healing assay. Results: HUVECs treated with 1 had the statistically significant decrease in tubular structure formation compared to the HUVECs treated with compounds 2-8. This effect was enhanced by co-treatment with inhibitors for phosphatidylinositol 3-kinase (PI3K) (LY294002) and extracellular signal-regulated kinase (ERK) (U0126). Treatment with 1 decreased the expression of phosphorylation of ERK, PI3K, vascular endothelial growth factor receptor2 (VEGFR2), Akt, and mammalian target of rapamycin (mTOR). In addition, the ability of A2780 cells to cover the scratched area were also decreased. This effect was enhanced by co-treatment with U0126. Lastly, treatment with 1 decreased the phosphorylation of ERK, matrix metalloproteinase-9 (MMP-9), and MMP-2. Conclusion: These results suggest that ginsenglactone A is a potential inhibitor of HUVEC tubular structure formation and A2780 cellular migration, which may be helpful for understanding its anticancer mechanism.