• BMB Reports
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• v.47 no.4
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• pp.227-232
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• 2014

Histone deacetylase-3 (HDAC3) is involved in cellular proliferation, apoptosis and transcriptional repression. However, the role of HDAC3 in angiogenesis remains unknown. HDAC3 negatively regulated the expression of angiogenic factors, such as VEGF and plasminogen activator inhibitor-1 (PAI-1). HDAC3 showed binding to promoter sequences of PAI-1. HDAC3 activity was necessary for the expression regulation of PAI-1 by HDAC3. VEGF decreased the expression of HDAC3, and the down-regulation of HDAC3 enhanced endothelial cell tube formation. HDAC3 negatively regulated tumor-induced angiogenic potential. We show the novel role of HDAC3 as a negative regulator of angiogenesis.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.145.2-145.2
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• 2003

Gardenia jasminoides Ellis has been used in traditional medicine for the treatment of inflammation, jaundice, headache, fever and hypertension. The 70％ ethanolic extract of gardenia fruit showed strong anti-angiogenic activity in the chick embryo chorioallantoic membrane (CAM) assay. Among hexane, ethyl acetate, n-butanol and aqueous fractions prepared from the 70％ ethanolic extract, the n-butanol fraction was found to be most effective in the CAM assay. (omitted)

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.165-170
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• 2017

Cordyceps bassiana is one of Cordyceps species with anti-oxidative, anti-cancer, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic, and anti-nociceptive activities. This mushroom has recently demonstrated to have an ability to reduce 2,4-dinitrofluorobenzene-induced atopic dermatitis symptoms in NC/Nga mice. In this study, we further examined phytochemical properties of this mushroom by column chromatography and HPLC analysis. By chromatographic separation and spectroscopic analysis, 8 compounds, such as 1,9-dimethylguanine (1), adenosine (2), uridine (3), nicotinamide (4), 3-methyluracil (5), 1,7-dimethylxanthine (6), nudifloric acid (7), and mannitol (8) were identified from 6 different fractions and 4 more subfractions. Through evaluation of their anti-inflammatory activities using reporter gene assay and mRNA analysis, compound 1 was found to block luciferase activity induced by $NF-{\kappa}B$ and AP-1, suppress the mRNA levels of cyclooxygenase (COX)-2 and tumor necrosis factor $(TNF)-{\alpha}$. Therefore, our data strongly suggests that compound 1 acts as one of major principles in Cordyceps bassiana with anti-inflammatory and anti-atopic dermatitis activities.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.112.2-112.2
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• 2000

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.557-562
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• 2006

Hypoxia induced angiogenesis and inflammation are essential processes for metastasis and progress of solid tumors. We examined the anti-angiogenic and inflammation related activity of Kochiae Fructus (KF) extract. To investigate the roles of the KF extract, we performed MTS assay, western blots using HaCaT cells and $HepG_2$ cells. The results are as follows. The protein level of $HIF-1{\alpha}$ was reduced when induced by $CoCl_2$ in $HepG_2$ cells treated with KF extract and induced by IGF-11 in HaCaT cells treated with KF extract. KF extract reduced the mRNA level of VEGF in HaCaT cells and KF extract reduced the protein level of iNOS in HaCaT cells. These results suggest that KF extract contributes to the anti-angiogenic and anti-inflammatory activities and also we could assume that KF extract act as antioxidant or anti-inflammatory agents via reduction of $HIF-1{\alpha}$.

• Journal of Microbiology and Biotechnology
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• v.28 no.8
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• pp.1332-1338
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• 2018

In the course of studies to discover natural products with anti-angiogenic properties, two cyclic octapeptides, octaminomycins A (1) and B (2), were isolated from the cultures of Streptomyces sp. RK85-270. Octaminomycins suppressed the vascular endothelial growth factor (VEGF)-induced proliferation, adhesion, tube formation, migration, and invasion of HUVECs. Anti-angiogenic activity was futher confirmed in vivo by the chicken chorioallantoic membrane assay. We also identified that 1 and 2 inhibited the phosphorylation of VEGF receptor 2, AKT, and ERK1/2 and the expression and activities of MMP-2 and MMP-9. These results suggest that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to angiogenesis-dependent diseases.

• Journal of Cancer Prevention
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• v.22 no.1
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• pp.1-5
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• 2017

Pancreatic cancer is a highly aggressive malignant tumor of the digestive system and radical resection, which is available to very few patients, might be the only possibility for cure. Since therapeutic choices are limited at the advanced stage, prevention is more important for reducing incidence in high-risk individuals with family history of pancreatic cancer. Epidemiological studies have shown that a high consumption of fish oil or ${\omega}3-polyunsaturated$ fatty acids reduces the risk of pancreatic cancers. Dietary fish oil supplementation has shown to suppress pancreatic cancer development in animal models. Previous experimental studies revealed that several hallmarks of cancer involved in the pathogenesis of pancreatic cancer, such as the resistance to apoptosis, hyper-proliferation with abnormal $Wnt/{\beta}-catenin$ signaling, expression of pro-angiogenic growth factors, and invasion. Docosahexaenoic acid (DHA) is a ${\omega}3-polyunsaturated$ fatty acid and rich in cold oceanic fish oil. DHA shows anti-cancer activity by inducing oxidative stress and apoptosis, inhibiting $Wnt/{\beta}-catenin$ signaling, and decreasing extracellular matrix degradation and expression of pro-angiogenic factors in pancreatic cancer cells. This review will summarize anti-cancer mechanism of DHA in pancreatic carcinogenesis based on the recent studies.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2081-2086
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• 2015

Gecko is a kind of traditional Chinese medicine with remarkable antineoplastic activity. However, undefined mechanisms and ambiguity regarding active ingredients limit new drug development from gecko. This study was conducted to assess anti-angiogenic properties of the aqueous extracts of fresh gecko (AG) or macromolecular components separated from AG (M-AG). An enzyme-linked immunosorbent assay (ELISA) approach was applied to detect the vascular endothelial growth factor (VEGF) secretion of the tumor cells treated with AG or M-AG. The effect of AG or M-AG on vascular endothelial cell proliferation and migratory ability was analyzed by tetrazolium dye colorimetric method, transwell and wound-healing assays. Chick embryo chorioallantoic membrane (CAM) assays were used to ensure the anti-angiogenic activity of M-AG in vivo. The results showed that AG or M-AG inhibited the VEGF secretion of tumor cells, the relative inhibition rates of AG and M-AG being 27.2% and 53.2% respectively at a concentration of $20{\mu}L/mL$. AG and M-AG inhibited the vascular endothelial (VE) cell proliferation with IC50 values of $11.5{\pm}0.5{\mu}L/mL$ and $12.9{\pm}0.4{\mu}L/mL$ respectively. The VE cell migration potential was inhibited significantly (p<0.01) by the AG (${\geq}24{\mu}L/mL$) or M-AG (${\geq}12\mu}L/mL$) treatment. In vivo, neovascularization of CAM treated with M-AG was inhibited significantly (p<0.05) at a concentration of ${\geq}0.4{\mu}L/mL$. This study provided evidence that anti-angiogenesis is one of the anti-tumor mechanisms of AG and M-AG, with the latter as a promising active component.

• 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.

• BMB Reports
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• v.31 no.5
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• pp.427-431
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• 1998

In the previous report (Choi et al., 1997), the angiogenin binding peptides identified from a phage-peptide library were analyzed by using the fusion proteins composed of the Escherichia coli maltose binding protein and its corresponding peptides. However, it was difficult to obtain a sufficient amount of the fusion proteins required for further analysis because of the low expression level. We now report a high level expression of the fusion protein and analysis of its anti-angiogenin activity. The use of strong T7 promoter and removal of signal sequence allowed about a 20-fold increase in the expression efficiency of the fusion protein. We were able to obtain about 10 mg of purified fusion protein from one liter of culture. The purified fusion protein showed angiogenin-specific affinity and inhibited the binding of biotinylated actin to human angiogenin at $IC_{50}$ of 0.6 mM. Its anti-angiogenin activity was also revealed by the chorioallantoic membrane assay.