• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.263-269
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• 2009

4-Hydroxybenzaldehyde, a phenolic compound found in a variety of natural sources, was previously shown to contain anti-inflammatory and related anti-angiogenic and anti-nociceptive activities. The present work was designed to assess some pharmacological activities of 2,4-dihydroxybenzaldehyde (DHD), an analogue of 4-hydroxybenzaldehyde. DHD exhibited a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis, and its $IC_{50}$ value was $2.4\;{\mu}g/egg$. DHD also contained in vivo anti-inflammatory activity using acetic acid-induced permeability and carrageenan-induced air pouch models in mice. In the air pouch model, DHD showed significant suppression in exudate volume, number of polymorphonuclear leukocytes and nitrite content. DHD showed an anti-nociceptive activity in the acetic acid-induced writhing test in mice. It also suppressed enhanced production of nitric oxide (NO) and elevated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. It was able to slightly decrease the level of reactive oxygen species in the stimulated macrophages. DHD at the used concentrations couldn't modulate the viabilities of RAW264.7 cells. Taken together, like 4-hydroxybenzaldehyde, DHD contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities.

• BMB Reports
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• v.34 no.3
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• pp.206-211
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• 2001

Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis and the growth of several primary tumors. However, the opinions on the activity of endostatin derivatives deleted N- or C- terminal are still controversial. In this regard, we produced mouse endostatin and its derivatives in the prokaryotic system, and studied their anti-tumor activity. The [$^3H$]-thymidine incorporation assay demonstrated that N-terminal deleted mouse endostatin, and a C- and N-terminal deleted mutant, effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs). The biological activity of endostatin was also shown by its in vivo anti-angiogenic ability on the chorioallantoic membrane (CAM) of a chick embryo. Treatment of $200\;{\mu}g$ of mouse endostatin, or N-terminal deleted mouse endostatin, inhibited capillary formation of CAM 45 to 71%, which is comparative to a 80% effect of positive control, $1\;{\mu}g$ of retinoic acid. An in vivo mouse tumor growth assay showed that N-terminal deleted mouse endostatin, and the N-/C-terminal deleted mutant, significantly repressed the growth of B16F10 melanoma cells in mice as did the full-length mouse endostatin. According to these results, N-and N-/C-terminal deleted mouse endostatins are the potent inhibitors of tumor growth and angiogenesis.

• Molecules and Cells
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• v.38 no.3
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• pp.273-278
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• 2015

The induction of angiogenesis is a crucial step in tumor progression, and therefore, efficient inhibition of angiogenesis is considered a powerful strategy for the treatment of cancer. In the present study, we report that the lipophilic antimicrobial peptides from EML-CAP3, a new endophytic bacterial strain isolated from red pepper leaf (Capsicum annuum L.), exhibit potent antiangiogenic activity both in vitro and in vivo. The newly obtained antimicrobial peptides effectively inhibited the proliferation of human umbilical vein endothelial cells at subtoxic doses. Furthermore, the peptides suppressed the in vitro characteristics of angiogenesis such as endothelial cell invasion and tube formation stimulated by vascular endothelial growth factor, as well as neovascularization of the chorioallantoic membrane of growing chick embryos in vivo without showing cytotoxicity. Notably, the angiostatic peptides blocked tumor cell-induced angiogenesis by suppressing the expression levels of hypoxia-inducible $factor-1{\alpha}$ and its target gene, vascular endothelial growth factor (VEGF). To our knowledge, our findings demonstrate for the first time that the antimicrobial peptides from EML-CAP3 possess antiangiogenic potential and may thus be used for the treatment of hypervascularized tumors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3113-3121
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• 2014

Colorectal cancer remains one of the most common types of cancer and a leading cause of cancer death worldwide. In this study, we aimed to investigate effects of DuP-697, an irreversible selective inhibitor of COX-2 on colorectal cancer cells alone and in combination with a promising new multi-targeted kinase inhibitor E7080. The HT29 colorectal cancer cell line was used. Real time cell analysis (xCELLigence system) was conducted to determine effects on colorectal cell proliferation, angiogenesis was assessed with a chorioallantoic membrane model and apoptosis was determined with annexin V staining. We found that DuP-697 alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. For the antiproliferative effect the half maximum inhibition concentration ($IC_{50}$) was $4.28{\times}10^{-8}mol/L$. Antiangiogenic scores were 1.2, 0.8 and 0.5 for 100, 10 and 1 nmol/L DuP-697 concentrations, respectively. We detected apoptosis in 52% of HT29 colorectal cancer cells after administration of 100 nmol/L DuP-697. Also in combination with the thyrosine kinase inhibitor E7080 strong antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells were observed. This study indicates that DuP-697 may be a promising agent in the treatment of colorectal cancer. Additionally the increased effects observed in the combination with thyrosine kinase inhibitor give the possibility to use lower doses of DuP-697 and E7080 which can avoid and/or minimize side effects.

• Journal of Korean Traditional Oncology
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• v.13 no.1
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• pp.13-24
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• 2008

Objective: To evaluate the effects of Bikihaun (BKH) on angiogenesis. Method: We examined the anti-angiogenic effect of BKH in invasion assay model. We performed proliferation assay, migration assay, tube formation assay and Chicken Chorioallantoic Membrane (CAM) assay. Results: In proliferation assay, at lower dose under 125 ${\mu}g/m{\ell}$ anti-angiogenesis effect of the group treated BKH made no difference with the control group. But, at the dose of 250 ${\mu}g/m{\ell}$ or more anti-angiogenesis effect of the group treated BKH showed more effective as compared to the control group. In migration assay, BKH did not affect migration of vascular endothelial cell. In tube formation assay, at lower dose under 100 ${\mu}g/m{\ell}$ showed mild effect of anti-tube formation. But, at the dose of 1000 ${\mu}g/m{\ell}$ showed more effective anti-tube formation. In CAM assay, BKH showed anti-angiogenesis effect at the dose of 10 ${\mu}g/m{\ell}$. Conclusion: BKH has antiangiogenetic properties in vitro.

• BMB Reports
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• v.49 no.9
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• pp.508-513
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• 2016

Hypoxia-inducible factor (HIF)-1α is a key regulator associated with tumorigenesis, angiogenesis, and metastasis. HIF-1α regulation under hypoxia has been highlighted as a promising therapeutic target in angiogenesis-related diseases. Here, we demonstrate that diacetyl atractylodiol (DAA) from Atractylodes japonica (A. japonica) is a potent HIF-1α inhibitor that inhibits the Akt signaling pathway. DAA dose-dependently inhibited hypoxia-induced HIF-1α and downregulated Akt signaling without affecting the stability of HIF-1α protein. Furthermore, DAA prevented hypoxia-mediated angiogenesis based on in vitro tube formation and in vivo chorioallantoic membrane (CAM) assays. Therefore, DAA might be useful for treatment of hypoxia-related tumorigenesis, including angiogenesis.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.72-78
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• 2013

This work aimed to assess some pharmacological activities of P. leptostachya var. asiatica Hara. The dried roots of P. leptostachya var. asiatica Hara were extracted with 70% ethanol to generate the powdered extract, named PLE. Anti-angiogenic activity was detected using chick chorioallantoic membrane (CAM) assay. In vitro anti-inflammatory activity was evaluated via analyzing nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and reactive oxygen species (ROS) level in the stimulated macrophage cells. Matrix metalloproteinase-9 (MMP-9) and -2 (MMP-2) activities in the culture media were detected using zymography. PLE exhibits an anti-angiogenic activity in the CAM assay, and displays an inhibitory action on the generation of NO in the LPS-stimulated macrophage cells. In the stimulated macrophage cells, it is able to diminish the enhanced ROS level. It can potently scavenge the stable DPPH free radical. It suppresses the induction of iNOS and COX-2 and the enhanced MMP-9 activity in the stimulated macrophage cells. Both monooxygenase and oxidase activities of tyrosinase were strongly inhibited by PLE. Taken together, the dried roots of P. leptostachya var. asiatica Hara possess anti-angiogenic, anti-inflammatory, antioxidant and skin whitening activities, which might partly provide its therapeutic efficacy in traditional medicine.

• Korean Journal of Poultry Science
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• v.12 no.2
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• pp.135-143
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• 1985

A total of eight strains of avian reoviruses were isolated from chickens with arthritis or stunted growth. The isolations were made from broilers or broiler breeders under 12 weeks of age. The viruses had a typical morphology of reoviruses with double capsid layers and 81nm of diameter. In agar gel precipitation tests, the isolates reacted with antisera prepared against S-1133 or R-1 strains of avian reoviruses and cross reacted with S-1133 antigen. They did not agglutinated RBC's from day-old chicks, adult chickens, guinea pigs, and horses. The isolates showed strong resistance against the treatments of chloroform, IUdR, and heat, When infectivities of the viruses were titrated in cell cultures of chicken embryo fibroblast, chicken embryo liver, and Vero cells, similar end points reached four to five days after inoculation, regardless of tell types and virus inoculation time, either inoculated simultaneously at the time of cell seeding or on confluency. Mean times of mortality of chicken embryos inoculated with the isolates via the chorioallantoic membrane ranged from 54 to 59 hours and that of S-1133 strain was 73 hours.

• KSBB Journal
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• v.29 no.1
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• pp.36-41
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• 2014

Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.

• The Korea Journal of Herbology
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• v.26 no.3
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• pp.83-90
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• 2011

Objectives : This study was performed to investigate the influence of black ginseng radix extracts (BG) and ginsenoside Rg3, Rg5 on basic fibroblast growth factor (bFGF) induced proliferation, migration and capillary tubule-like formation of human umbilical vein endothelial cells (HUVECs). Methods : HUVECs were cultured with BG and ginsenoside Rg3, Rg5 at different concentrations (60, 125, 250, 500, $1,000{\mu}g/m\ell$) for 2 day In the presence of bFGF, respectively. XTT was used to detect the proliferation. Migration and tube formations were examined to detect the antiangiogenesis. Also, the chick embryo chorioallantoic membrane (CAM) assay was performed to detect the antiangiogenesis. Results : BG and ginsenoside Rg3, Rg5 significantly inhibited bFGF-induced endothelial cell proliferation and migration in a dose-dependent manner. Tube formation in bFGF-induced HUVECs were suppressed by BG and ginsenoside Rg3, Rg5. Moreover, BG and ginsenoside Rg3, Rg5 (30-$50{\mu}g$/egg) inhibited new blood vessel formation on the growing CAM. Conclusions:Based on the present results, it can be suggested that BG has a potential chemopreventive agent via antiangiogenesis.