• KSBB Journal
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• v.24 no.6
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• pp.541-548
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• 2009

For investigation of anti-angiogenesis mechanism of Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus, anti-cell adhesion experiment was performed. The adhesion of U937 cells to IL-$1\beta$-stimulated HUVECs was completely suppressed by 276% at 0.2 mg/L of Anthrisci radix, 220% at 5 mg/L of Psoraleae semen, 158% at 10 mg/L of Siegesbeckiae herba and 132% at 20 mg/L of Corni fructus, respectively. And the adhesion of PMA-chemical stimulated U937 cells to HUVECs, it was inhibited 139% at 0.2 mg/L of Anthrisci radix, 442% at 5 mg/L of Psoraleae semen, 720% at 10 mg/L of Siegesbeckiae herba and 664% at 20 mg/L of Corni fructus. Also, the adhesion of chemical stimulated U937 cells to IL-$1\beta$/chemical stimullated HUVECs, it was inhibited by 286% at 0.2 mg/L of Anthrisci radix, 146% at 5 mg/L of Psoraleae semen, 436% at 10 mg/L of Siegesbeckiae herba and 297% at 20 mg/L of Corni fructus, respectively. It would be a useful substance for anti-cell adhesion based on anti-angiogenesis for anti-obesity and anti-cancer.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.4
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• pp.329-336
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• 2016

Cutaneous microvasculature plays a critical role in age-associated skin changes. A considerable reduction of number and size of vessels has been observed in the upper dermis of elderly skin. Forsythiae fructus (FF), the dried fruit of plant Forsythia suspensa (F. suspensa), has been traditionally used as an herbal medicine to treat inflammatory diseases and bacterial diseases. However, its regulatory effect on angiogenic responses has not been elucidated in skin. Therefore, we analyzed secretory profiles upon treatment of FF extract using array designed to detect angiogenesis-associated mediators in human keratinocytes. Because keratinocyte-derived VEGF (vascular endothelial growth factor) has been regarded as a potent factor for new microvasculature under the epidermis, we further investigated the effect of FF extract on VEGF production. We observed that the VEGF expression of mRNA and protein level was increased by about 2 folds in a dose-dependent manner after FF extract treatment. In signaling experiments, FF extract induced rapid p38 MAPK activation within 5 min, and the activation was totally abrogated by pretreatment with a p38 MAPK specific inhibitor. The FF-induced VEGF upregulation was also significantly attenuated by a p38 MAPK inhibition. Taken together, FF extract induces VEGF production via p38 MAPK activation in human epidermal keratinocytes. These novel findings suggest that FF is useful as a potential agent with pro-angiogenic activity and may help to improve age-dependent reduction of the microvasculature in aged skin or to heal skin wound.

• Korean Journal of Food Science and Technology
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• v.43 no.2
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• pp.206-212
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• 2011

Makgeolli is Korean traditional alcoholic beverage that has historically been brewed. In this study, we analyzed the profile of organic acids in makgeolli and also evaluated its physiological characteristics. Makgeolli contained excess lactic acid, which is produced by lactic acid bacteria (LAB). Anti-obesity effects of makgeolli were investigated in 3T3-L1 preadipocytes. Compared to the negative control, makgeolli inhibited the differentiation of preadipocyte as quantified by Oil red O dye. In particular, $100{\mu}g/mL$ makgeolli reduced 40 to 70% of differentiation. To evaluate the anti-angiogenic and anti-inflammatory effects of makgeolli, we performed chorioallantoic membrane assay and measured nitric oxide production from lipopolysaccharide-induced RAW264.7 cells. Most makgeolli interrupted the formation of neo-vasculature and significantly inhibited NO production in a dose-dependent manner. Taken together, these findings suggest that commercial makgeolli has inhibitory activities against adipogenesis, neo-vascularization, and inflammation, and also they are influenced by second metabolites from nuruk microflora containing fungi and LAB.

• Journal of Life Science
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• v.22 no.1
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• pp.41-48
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• 2012

Bee venom (BV) has been used in medicine to treat a variety of diseases including arthritis, rheumatism, and various cancers. Recent reports indicate that BV has anti-angiogenic effects, but the precise molecular mechanism underlying the effects of BV against colorectal cancer remains to be elucidated. We examined the effects of BV and its major components (melittin and apamin) on tumor angiogenesis and found that BV significantly decreased protein levels of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), an important factor involved in angiogenesis and tumor progression, in human colorectal carcinoma HCT116 cells. BV also suppressed the transcription of HIF-$1{\alpha}$ under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major target gene of HIF-$1{\alpha}$. We also found that these effects were mainly elicited by apamin, but not melittin. BV specifically inhibited the phosphorylation of ERK1/2 without changing the total levels of this protein, but had no effect on kinases of p38/JNK and AKT. Our results suggest that BV may inhibit human colorectal cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$ and VEGF expression, thereby providing a novel potential mechanism for the anticancer action of BV.

• Korean Journal of Food Science and Technology
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• v.48 no.1
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• pp.66-71
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• 2016

Delphinidin is a blue-red pigment and one of the major anthocyanins in plants. It plays an important role in anti-oxidant, anti-inflammatory, anti-mutagenic and anti-cancer properties. In this study, we investigated the inhibitory effects of delphinidin on vascular endothelial growth factor (VEGF) gene expression, an important factor involved in angiogenesis and tumor progression in human prostate cancer. Delphinidin decreased levels of epidermal growth factor (EGF)-induced VEGF mRNA expression in PC-3M cells. The expression of the EGF-induced hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and signaling transducer and activator of transcription 3 (STAT3) proteins, which are the major transcription factors for VEGF, were inhibited by delphinidin. In addition, delphinidin decreases HRE-promoter reporter gene activity, suggesting that delphinidin can suppress the transcription of HIF-$1{\alpha}$ under EGF induction, leading to a decrease in the expression of VEGF. Delphinidin specifically suppressed the phosphorylation of Akt, p70S6K, and 4EBP1, but not the phosphorylation of EGFR. Therefore, our results suggest that delphinidin may inhibit human prostate cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$, STAT3 and VEGF gene expression.

• Journal of Life Science
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• v.14 no.5
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• pp.874-881
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• 2004

Angiogenesis has been implicated in progression of inflammation, arthritis, psoriasis, atherosclerosis as well as tumor growth and metastasis. Intensive studies have been carried out to develop a strategy for cancer treatment by blocking angiogenesis. During angiogenesis, endothelial proliferation and migration essentially occurs upon activation. In this study, we compared the expression profiles of human umbilical endothelial cells activated by incubating in vitro in the rich medium containing several growth factors, and non-activated ones. cDNA targets derived from total RNAs of HUVEC activated for 13 h in M199 medium containing endothelial cell growth supplement, 20% fetal bovine serum, and heparin, after reaching 70～80% confluency, or non-activated, were hybridized onto oligonucleotide microarrays containing 1,8864 genetic elements. Unsupervised hierarchical clustering analysis resulted in two subgroups on dendrogram exhibiting activated and non-activated HUVECs. We then extracted 122 outlier genes which were shown to be up-regulated or under-expressed by at least 2-folds in activated HUVECs. Among these, 32 annotated genes were up-regulated and 38 were down-regulated in activated HUVECs. Interestingly, genes involved in cell proliferation, motility, and inflammation/ immune response were up-regulated in activated HUVEC, whereas genes for cell adhesion or vessel morphogenesis/function were down-regulated. Unexpectedly, the expression of genes well-characterized as angiogenesis markers was not changed except Eph-B4, which was down-regulated about 4 folds. 52 unknown genes were also up- or down-regulated. Therefore, these results could provide an opportunity to targeting new vascular molecules for the development of anti-angiogenic molecules.

• KSBB Journal
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• v.25 no.3
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• pp.265-270
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• 2010

Simvastatins are widely used to reduce endogenous cholesterol synthesis and improve hypercholesterolemia. Also, simvastatin have been shown to induce both angiogenic and angiostatic responses. In this study, It was attempted to resolve this controversy by studying the effects of simvastatin on the cell migration and invasion with the proteinases secretion and expression pattern. U-373-MG cells treated with low dose of simvastatin ($0.001{\sim}0.5\;{\mu}M$) showed the induction of migration and invasion compared with the addition of a control buffer. On the contrary, high dose of simvastatin ($1{\sim}20\;{\mu}M$) showed the reduction of migration and invasion compared with the addition of a control buffer. It was also showed that simvastatin-regulated migrative and invasive phenotypes were consistent with the secretion and expression pattern of matrix metalloproteinase-2 (MMP-2), MMP-9 and plasmin.

• Journal of Chest Surgery
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• v.32 no.2
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• pp.151-157
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• 1999

Background: Increasing evidences from experimental studies indicate that apoptosis may be inversely related to angiogenesis in tumor progression. Material and Method: To explore how apoptosis correlates with tumor angiogenesis, we measured the apoptotic index(AI) using the terminal deoxynucleotidyl transferase method(Apop Tag In Situ Apoptosis Detection Kit, ONCOR) and the intratumoral microvessel density using the anti-CD31 monoclonal antibody in non-small cell lung cancer. Result: Statistical analysis revealed an inverse correlation between AIs and intratumoral microvessel densities in squamous cell lung carcinoma(Spearman rank correlation coefficient r=- 0.229, p=0.047). Conclusion: The results of this study demonstrated that the amount of apoptosis in squamous cell lung carcinoma may be influenced by the extent of neovascularization. This suggests that tumor angiogenesis may contribute to a reduction of apoptosis in tumor cells.

• Journal of Life Science
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• v.23 no.1
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• pp.131-136
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• 2013

Sirtuin proteins have emerged as important modulators of several age-associated diseases. These include cancer and diabetes, as well as cardiovascular and neurodegenerative diseases. Among the sirtuin family members, SIRT2 mRNA is strongly expressed. To investigate the pathophysiological significance of SIRT2 as a primary regulator of angiogenesis, we focused on the biological role of SIRT2 under hypoxic conditions, examining the gene expression pattern of sirtuin family members in human umbilical vein endothelial cells (HUVECs). SIRT2 was expressed primarily in the cytoplasm, but it was dynamically trans-localized in the nuclear by hypoxia stimuli. Interestingly, both SIRT2 and the pro-angiogenic factor, VEGF, were up- regulated by hypoxia. A Matrigel assay demonstrated that the HUVECs formed a tube-like structure under hypoxia. The SIRT2 inhibitor, AK-1, significantly decreased the tube-forming activity of the HUVECs under either normoxia or hypoxia conditions. These findings suggest that SIRT2 might be a key regulator of angiogenesis.

• 한국약용작물학회:학술대회논문집
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• 2008.11a
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• pp.445-446
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• 2008