• Korean Journal of Environmental Biology
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• v.28 no.1
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• pp.14-19
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• 2010

Angiogenesis is an important event involved in cell growth and wound healing process. However, the imbalance of growth factors causes diseases, such as ocular, inflammatory diseases. One of treatment of these diseases is to suppress the formation of blood vessels. Function and mechanism of gold nanoparticles (AuNPs) in the formation of blood vessels is not yet proved. Pigment epithelium derived factor (PEDF) is currently being offered anti-angiogenic materials. In this study, we postulated that AuNPs might have the ability to inhibit angiogenesis, the pivotal step in tumor growth, invasion and metastasis. We have demonstrated that AuNPs could inhibit vascular endothelial growth factor (VEGF) induced cell proliferation, angiogenesis in bovine retinal endothelial cells.

• Journal of Life Science
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• v.26 no.1
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• pp.91-100
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• 2016

Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an attractive therapeutic approach for the treatment of angiogenic diseases such as cancer. However, uncontrolled angiogenesis is also necessary for tumor development and metastasis. Inhibition of vascular endothelial growth factor (VEGF) signaling, a critical factor in the induction of angiogenesis, cause robust and rapid changes in blood vessels of tumors and therefore VEGF constitutes a target for such anti-angiogenic therapy. Recently, since natural compounds pose significantly less risk of deleterious side effects than synthetic compounds, a great many natural resources have been assessed for useful substance for anti-angiogenic treatment. Here we evaluated the anti-angiogenic effects of a hot water extract of Scutellaria baicalensis (SBHWE) using in vitro assays and ex vivo animal experiments. Our results show that SBHWE dose-dependently abrogated vascular endothelial responses by inhibiting VEGF-stimulated migration and invasion as well as tube formation in a human umbilical vein endothelial cell (HUVEC) model, without cytotoxicity, as determined by a cell viability assay. Further study revealed that SBHWE prevented VEGF-induced neo-vascularization in a rat aortic ring sprouting model. Taken together, our findings reveal an anti-angiogenic activity of Scutellaria baicalensis and suggest that SBHWE is a novel candidate inhibitor of VEGF-induced angiogenesis.

• Journal of Life Science
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• v.24 no.12
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• pp.1345-1355
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• 2014

The interruption of angiogenesis using herbal extracts is now recognized as a useful approach for treating many solid tumors. To date, the best-validated antitumor approach is to target the vascular endothelial growth factor (VEGF)-induced angiogenic pathway. In the present study, we first identified the antiangiogenic activity of a hot-water extract of Rubus coreanus Miquel (RCMHE) in vitro and ex vivo. This extract suppressed VEGF-induced angiogenesis, the phosphorylation of extracellular regulated kinase (ERK), p38 and the activation of matrix metalloproteinases (MMPs). RCMHE also inhibited the VEGF-responsive phosphorylation of VEGFR2. These results clearly show that RCMHE may have potential therapeutic value for angiogenesis-associated human diseases through the suppression of angiogenesis and the interruption of the phosphorylation of VEGFR2.

• Journal of Life Science
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• v.34 no.6
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• pp.399-407
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• 2024

Angiogenesis is the process by which new blood vessels form from existing blood vessels. This phenomenon occurs during growth, healing, and menstrual cycle changes. Angiogenesis is a complex and multifaceted process that is important for the continued growth of primary tumors, metastasis promotion, the support of metastatic tumors, and cancer progression. Impaired angiogenesis can lead to cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. Currently, there are only a handful of effective antiangiogenic drugs. Recent studies have shown that natural marine products exhibit antiangiogenic effects. In a previous study, we reported that the hexane extract of H. fusiformis (HFH) could inhibit the development of new blood vessels both in vitro and in vivo. The aim of this study was to describe the inhibitory effect of chloroform extracts of H. fusiformis on angiogenesis. To investigate how chloroform extract prevents blood vessel growth, we examined its effects on HUVEC, including cell migration, invasion, and tube formation. In a mouse Matrigel plug assay, H. fusiformis chloroform extract (HFC) also inhibited angiogenesis in vivo. Certain proteins associated with blood vessel growth were reduced after HFC treatment. These proteins include vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal transduction kinase, and serine/threonine kinase 1 (AKT). These studies have shown that the chloroform extract of H. fusiformis can inhibit blood vessel growth both in vitro and in vivo.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.191-199
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• 2005

Background: Though infections of Helicobacter pylori (H. pylori) are closely associated with activation of host angiogenesis, the underlying mechanisms, as well as the strategy for its prevention, have not been identified. Here, we investigated a causal role of H. pylori infection in angiogenesis of gastric mucosa and a potent inhibitory effect of a gastric proton pump inhibitor (PPI) on the gastropathy. Materials and Methods: A comparative analysis of CD 34 expression in tissues obtained from 20 H. pylori-associated gastritis and 18 H. pylori-negative gastritis patients was performed. Expression of $HIF-1{\alpha}$ and VEGF were tested by using RT-PCR. To evaluate the direct effect of H. pylori infection on differentiation of endothelial HUVEC cells, we carried out an in vitro angiogenesis assay. Results: H. pyfori-associated gastritis tissues showed significantly higher density of $CD34^+$ blood vessels than did H. pylori-negative gastritis tissues, and the levels were well correlated with expressions of $HIF-1{\alpha}$. Conditioned media from H. pylori-infected gastric mucosal cells stimulated a tubular formation of HUVEC cells. We also found a significant inhibitory effect of PPI, an agent frequently used for H. pylori eradication, on H. pylori-induced angiogenesis. This drug effectively inhibited the phosphorylation of MAP kinase ERK1/2, which is a principal signal for H. pylori-induced angiogenesis. Conclusion: The fact that PPls can down-regulate H. pylori-induced angiogenesis suggest that anti-angiogenic treatment using PPI may be a preventive approach for H. pylori-associated carcinogenesis.

• Applied Biological Chemistry
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• v.46 no.1
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• pp.50-54
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• 2003

Polygonum cuspidatum has been used as a fork medicine for a long time. Emodin was purified from the root of P. cuspidatum by thin layer chromatography (TLC) and preparative high perfomance liquid chromatography (HPLC). The effects of emodin on the migration of endothelial cells and in vitro angiogenesis stimulated with vascular endothelial cell growth factor (VEGF) were examined, using human umbilical vein endothelial cells (HUVECs) and porcine pulmonary arterial endothelial cells (PPAECs). Emodin potently inhibited the VEGF-induced migration of (HUVECs) at relatively low cocentrations $(0.1-10\;{\mu}g/ml)$; the inhibition of endothelial cells by emodin was 75.4% at $0.1\;{\mu}g/ml$ and about 90% at $1\;{\mu}g/ml$. Emodin also inhibited VEGF-induced sprout formation in vitro at concentrations of $0.1-10\;{\mu}g/ml$. Emodin was also evaluated for the inhibitory potential on in vivo angiogenesis in a growing chick embryo chorioallantoic membranes (CAM). At a concentration of $1.0\;{\mu}g/ml$ Per disc, emodin was able to induce avacular zone in the CAMs. These findings suggest that emodin is a potent angiogenesis inhibitor and P. cuspidatum is a useful herb in the development of therapeutics for angiogenesis dependent diseases.

• Journal of Life Science
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• v.31 no.1
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• pp.59-65
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• 2021

Prunus mume Sieb. et Zucc is distributed throughout Asia and has traditionally been used as medicine and food. P. mume is known to contain large amounts of various organic acids, minerals, and phenol components. To date, the trend of P. mume research has focused only on the effects of antioxidant, anticancer and antibacterial, with only a few studies have focused on angiogenesis. Angiogenesis is a common characteristic of metastatic cancer through which oxygen and nutrients are delivered to the cells and tissues. In the present study, angiogenesis-inhibiting activity was investigated by evaluating the total polyphenol and flavonoid contents of the P. mume butanol fraction (PBF) and their ability to inhibit VEGF-induced human umbilical vein endothelial cells (HUVECs) proliferation, migration, invasion, and capillary formation. The polyphenols (12.81 mg GAE/g) and flavonoids (28.4 mg QE/g) of the PBF exhibited high antioxidant activity. The results of this study showed that PBF did not inhibit the proliferation of HUVECs at concentrations of 25-200 ㎍/ml and did not exhibit toxicity to normal cells. However, PBF inhibited the VEGF-induced mobility, invasion, and capillary formation of HUVECs. These results show that PBF inhibits the angiogenesis of HUVECs induced by VEGF. Therefore, PBF could serve as a therapeutic agent for the inhibition of angiogenesis.

• Journal of Life Science
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• v.27 no.9
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• pp.1059-1063
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• 2017

Angiogenesis is an essential step in tumoral growth and metastasis and is regulated by a balance between stimulators and inhibitors. Recently, antiangiogenic target therapy has shown promise as a new type of chemotherapy. Natural products have attracted widespread attention worldwide as a useful source of novel therapeutic compounds. The balloon-flower has long been used as a traditional medicinal material and food in Asia. In this study, we investigated whether extract of balloon-flower would inhibit in vitro angiogenesis and vascular-like network formation in human umbilical vein endothelial cells (HUVECs). The extract of Balloon-flower did not affect the viability of HUVECs. However, treatment with the Balloon-flower extract suppressed tube formation of HUVECs. In addition, after treatment with the Balloon-flower extract, cell migration decreased about 80%, and cell invasion was almost completely inhibited. Taken together, these results suggest that extract of Balloon-flower may have potential as an angiogenic inhibitor and that it could be developed as an anticancer agent.

• Journal of Life Science
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• v.25 no.6
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• pp.693-702
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• 2015

Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

• Journal of Life Science
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• v.25 no.2
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• pp.231-236
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• 2015

Angiotensin II (AngII) is an essential hormone that affects vascular physiology. For example, stimulation of vascular smooth muscle cells (VSMCs) rapidly induces vasoconstriction and results in the up-regulation of blood pressure. Chronic stimulation of VSMCs with AngII also results in hypertrophy. In this study, we confirmed an involvement of phosphatidylinositol 3-kinase (PI3K)-dependent calcium mobilization in AngII-induced generation of reactive oxygen species (ROS). Stimulation of rat aortic smooth muscle cells (RASMCs) with AngII significantly induced the generation of ROS in a dose- and time-dependent manner. AngII-induced generation of ROS was completely abolished by pharmacological inhibition of PI3K (with LY294002), but inhibition of the ERK signaling pathway had no effect. AngII-induced calcium mobilization was completely blocked by inhibition of PI3K, whereas inhibition of the ERK signaling pathway by PD98059 was ineffective. Depletion of extracellular calcium or inhibition of the L-type calcium channel by nifedipine completely blocked AngII-induced calcium mobilization. Depletion of extracellular calcium by EGTA and incubation of RASMCs with calcium-free medium both significantly blocked AngII-induced ROS generation. Inhibition of the L-type calcium channel also significantly blocked AngII-induced ROS generation. These results suggest that AngII-induced ROS generation is regulated by calcium mobilization, which, in turn, is modulated by a PI3K/L-type calcium channel signaling pathway.