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

• Journal of Haehwa Medicine
• /
• v.27 no.2
• /
• pp.11-20
• /
• 2018

Objectives : Coronary and cerebrovascular disease with high mortality is a major factor in arteriosclerosis. Pro-inflammatory cytokines damage vascular endothelial cells, leading to vascular inflammation. These vascular inflammation can build up cholesterol and thrombus to cause atherosclerosis. Methods : In this study, we researched the effect of ChungHyul-Plus for vascular inflammation in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). Change in mRNA expression of inflammatory cytokines (CCL5, CXCL8, CX3CL1, and MCP-1), cell adhesion molecules (VCAM-1 and ICAM-1), and anti-inflammation modulators (KLF2 and eNOS) were quantified by qRT-PCR. Results : ChungHyul-Plus decreased expression of inflammatory cytokines and cell adhesion molecules and increased anti-inflammation modulators expression in $TNF-{\alpha}$ stimulated HUVECs. Conclusions : These results suggest that ChungHyul-Plus can be used in the treatment and prevention of vascular inflammation and arteriosclerosis.

• Natural Product Sciences
• /
• v.18 no.4
• /
• pp.266-272
• /
• 2012

Hyperglycemia or high glucose (HG), is the hallmark of diabetes, known to induce oxidative stress, release of chemokines, and cytokines, which confer endothelial cell damage. On the other hand, microbial transformation of organic materials often leads to certain changes in their product structures which could enhance their biological activities. The aim of this study was to investigate the beneficial effects of fermented Gastrodia elata (FGE) in HG induced human umbilical vein endothelial cells (HUVECs) dysfunction. GE, fermented by Saccharomyces cerevisiae, which has an extensive history of safe use, exhibited higher phenolic compounds content than those of Gastrodia elata (GE). The HG-induced production of nitric oxide (NO) and interleukin-8 (IL-8) were significantly attenuated by FGE pretreatment to the cells, in a concentration dependent manner. In addition, FGE showed marked activity in free radical scavenging. These results suggest that FGE possesses beneficial effects in protecting against the oxidative stress, and inflammatory conditions in endothelial cells, caused by HG.

• Molecules and Cells
• /
• v.22 no.1
• /
• pp.70-77
• /
• 2006

Platelets are anucleate cytoplasmic fragments derived from bone marrow megakaryocytes, and endothelial cells constitute the barrier between bloodstream and adjacent tissues. Although platelets are thought to regulate the biological functions of endothelial cells, the molecular mechanisms involved are poorly understood. With human umbilical vein endothelial cells and freshly isolated platelets, we established an in vitro model of platelet-induced endothelial cell proliferation. Platelets stimulated endothelial cell proliferation in a dose-dependent manner and transwell experiments with semi-permeable membranes suggested that direct cell-to-cell contacts were required. We developed mAbs against platelets and selected a mAb that blocks their proliferative effect. We purified the antigen by immunoprecipitation and identified it by Q-TOF MS analysis as the tetraspanin CD9. Since both platelets and endothelial cells expressed CD9 strongly on their surfaces we carried out a pre-treatment experiment that showed that CD9 molecules on the endothelial cells participate in the mitogenic effect of the platelets. The inhibitory effect of our mAb was comparable to that of a well-known functional anti-CD9 mAb. These results suggest that the tetraspanin CD9 plays an important role in endothelial regeneration.

• Biomolecules & Therapeutics
• /
• v.25 no.2
• /
• pp.158-164
• /
• 2017

Methylglyoxal (MGO) is a highly reactive metabolite of glucose which is known to cause damage and induce apoptosis in endothelial cells. Endothelial cell damage is implicated in the progression of diabetes-associated complications and atherosclerosis. Hypericin, a naphthodianthrone isolated from Hypericum perforatum L. (St. John's Wort), is a potent and selective inhibitor of protein kinase C and is reported to reduce neuropathic pain. In this work, we investigated the protective effect of hypericin on MGO-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Hypericin showed significant anti-apoptotic activity in MGO-treated HUVECs. Pretreatment with hypericin significantly inhibited MGO-induced changes in cell morphology, cell death, and production of intracellular reactive oxygen species. Hypericin prevented MGO-induced apoptosis in HUVECs by increasing Bcl-2 expression and decreasing Bax expression. MGO was found to activate mitogen-activated protein kinases (MAPKs). Pretreatment with hypericin strongly inhibited the activation of MAPKs, including P38, JNK, and ERK1/2. Interestingly, hypericin also inhibited the formation of AGEs. These findings suggest that hypericin may be an effective regulator of MGO-induced apoptosis. In conclusion, hypericin downregulated the formation of AGEs and ameliorated MGO-induced dysfunction in human endothelial cells.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.40 no.5
• /
• pp.635-641
• /
• 2011

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved with suppressed oxidative stress, cell adhesion molecules, and pro-inflammatory factors. The aim of this study was to determine whether green tea seed coat ethyl acetate fraction (GTSCE) could modulate cell adhesion molecules and inflammatory mediators in HUVEC stimulated with TNF-${\alpha}$. Nitric oxide (NO) production was significantly increased in TNF-${\alpha}$-stimulated HUVEC compared to TNF-${\alpha}$ only treated cells. The NO that is produced by endothelial nitric oxide synthase dilates blood vessels and has protective effects against platelet and leucocyte adhesion. GTSCE at 25, 50, 75, and $100\;{\mu}g$/mL significantly (p<0.05) reduced TNF-${\alpha}$ production. GTSCE significantly (p<0.05) inhibited soluble vascular cell adhesion molecule-1 level, in a dose-dependent manner. Monocyte chemoattractant protein-1 level was also significantly (p<0.05) inhibited by GTSCE treatment at $75\;{\mu}g$/mL compared to the TNF-${\alpha}$-only treated group. Total antioxidant capacity by GTSCE was significantly (p<0.05) enhanced compared to the TNF-${\alpha}$-only treated group. These results suggest that GTSCE can inhibit the production of cell adhesion molecules and inflammatory mediators and could be used as a candidate bioactive material to prevent the development of atherosclerosis.

• Korean Journal of Environmental Biology
• /
• v.27 no.1
• /
• pp.88-94
• /
• 2009

The process of atherosclerosis begins through secretion of inflammatory cytokine or adhesion of leukocyte from damage in blood vessels and transmigration. This study was conducted to investigate the effects of delphinidin chloride (DC) in the initial process of atherosclerosis on the expression of ICAM-1 (Intracellular Adhesion Molecule-1) and VCAM-1 (Vascular Adhesion Molecule-1) related to adhesion of leukocyte at the HUVEC (human umbilical vein endothelial cell line. As a result, cell growth inhibition rate at 50 ${\mu}M$ was respectively 4, 3 and 5% without cell toxicity. As a result of morphological observation monocyte-endothelial cell adhesion assay and optical microscope carried out to measure attachment of mononuclear cells to endothelial cells induced by Tumor necrosis factor-alpha (TNF-$\alpha$) at concentrations without cell toxicity, DC concentration-dependently suppressed attachment. When effects on the expression of VCAM-1 and ICAM-1, cell adhesion molecules induced from endothelial cells by TNF-$\alpha$, were comparatively analyzed using western blot analysis and RT-PCR methods, protein of VCAM-1 and ICAM-1 and expression at the level of mRNA were concentration-dependently reduced. Taken together, the results of this studies provide evidence that DC possess an anti-metastatic activity.

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

• The Korean Journal of Physiology and Pharmacology
• /
• v.23 no.5
• /
• pp.345-356
• /
• 2019

Docosahexaenoic acid (DHA), an omega-3-fatty acid, modulates multiple cellular functions. In this study, we addressed the effects of DHA on human umbilical vein endothelial cell calcium transient and endothelial nitric oxide synthase (eNOS) phosphorylation under control and adenosine triphosphate (ATP, $100{\mu}M$) stimulated conditions. Cells were treated for 48 h with DHA concentrations from 3 to $50{\mu}M$. Calcium transient was measured using the fluorescent dye Fura-2-AM and eNOS phosphorylation was addressed by western blot. DHA dose-dependently reduced the ATP stimulated $Ca^{2+}$-transient. This effect was preserved in the presence of BAPTA (10 and $20{\mu}M$) which chelated the intracellular calcium, but eliminated after withdrawal of extracellular calcium, application of 2-aminoethoxy-diphenylborane ($75{\mu}M$) to inhibit store-operated calcium channel or thapsigargin ($2{\mu}M$) to delete calcium store. In addition, DHA ($12{\mu}M$) increased ser1177/thr495 phosphorylation of eNOS under baseline conditions but had no significant effect on this ratio under conditions of ATP stimulation. In conclusion, DHA dose-dependently inhibited the ATP-induced calcium transient, probably via store-operated calcium channels. Furthermore, DHA changed eNOS phosphorylation suggesting activation of the enzyme. Hence, DHA may shift the regulation of eNOS away from a $Ca^{2+}$ activated mode to a preferentially controlled phosphorylation mode.

• BMB Reports
• /
• v.42 no.10
• /
• pp.685-690
• /
• 2009

Angiogenesis is essential for tumor growth and vascular endothelial cell growth factor (VEGF) plays a key role in this process. Conversely, sphingosine 1-phosphate (S1P) is a biologically active sphingolipid known to play a key role in cancer progression by regulating endothelial cell proliferation and migration. In this study, the authors found that S1P increases the level of VEGF mRNA in human umbilical vein endothelial cells (HUVECs) and immortalized HUVECs (iHUVECs). Additionally, S1P was found to increase VEGF promoter activity in MS-1 mouse pancreatic islet endothelial cells. Furthermore, a pharmacological inhibitory study revealed that $G_{\alpha i/o}$-mediated phospholipase C, Akt, Erk, and p38 MAPK signaling are involved in this S1P-induced expression of VEGF. A component of AP1 transcription factor is important for S1P-induced VEGF expression. Taken together, these findings suggest that S1P enhances endothelial cell proliferation and migrat ion by upregulating the expression of VEGF mRNA.