• Korean Journal of Pharmacognosy
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• v.37 no.4 s.147
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• pp.253-257
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• 2006

We examined anti-angiogenic effects of water extracts from 32 plant materials (20 Korean medicinal plants and 12 western herbs) using cell-based anti-angiogenic assay, HUVEC tube formation assay, and then we found that 7 plant extracts inhibited HUVEC tube formation strongly. The plant materials which showed anti-angiogenic effects are Cinnamomi Ramulus, Atractylodis Rhizoma alba, Polygalae Radix, Myristicae Semen, Artemisiae Iwayomogii Herba, leaves of Rosmarinus officinalis, and leaves of Melissa officinalis. We also investigated inhibitory effects of these anti-angiogenic herbal extracts on MMP (matrix metalloproteinase) activity which has important roles in angiogenesis. Among extracts tested in this study, water extract of Melissa officinalis showed the most potent anti-angiogenic and MMP inhibitory activity.

• Bulletin of the Korean Chemical Society
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• v.26 no.4
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• pp.619-628
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• 2005

We attempted to replace a benzopyran ring of 4-[(N-imidazol-2-ylmethyl)-4-chloroanilino]benzopyran, previously discovered as anti-angiogenic agent with antitumor activity, with pyranopyridines. The [3,2-c]-, [3,2-b]-, [2,3-c]-, and [2,3-b]-pyranopyridines with -(imidazol-2-ylmethyl)aniline moiety at the 4-position, were synthesized respectively, and evaluated for primary anti-angiogenic properties through primary cultured HUVEC tube formation assay. From this study, we found that the pyranopyridine ring, especially [3,2-b]- and [2,3-c]-isomer, can replace the benzopyran ring of the compound 1 and can be optimized through the introduction of substituents both on the pyranopyridine ring and the aniline moiety for the identification of a novel anti-angiogenic agent.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.89-94
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• 2007

Ginseng is a widely-used alternative medicine for the treatment of cancer, diabetes, and cardiovascular diseases. Active components of P. ginseng, absorbed through gastrointestinal tract are the fermented ginsenosides by intestinal microorganisms. In the present study, we investigated the inhibitory effects of fermented ginseng with bifidobacterium (FGb) on the angiogenesis by analyzing in vitro tube formation and invasion assay using human umbilical vein endothelial cells (HUVECs), and in vivo angiogenesis using chick chorioallantoic membrane (CAM) assay. Treatment with FGb inhibited tube-like structure formation in a concentration-dependent manner. In addition, FGb significantly suppressed HUVEC invasion through Matrigel. Moreover, FGb dosedependently inhibited VEGF-induced angiogenesis in a CAM assay. These results suggest that FGb is a valuable anti-angiogenic remedy.

• Journal of Haehwa Medicine
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• v.25 no.1
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• pp.145-153
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• 2016

Objectives : The purpose of this study is to evaluate the wound healing potential of Glycyrrhiza uralensis extract. Methods : Free radical scavenging activity tests for DPPH, peroxynitrite (ONOO) and hydroxyl radical (${\cdot}OH$) and total phenolic contents of Glycyrrhiza uralensis extract were conducted. Tube formation assay was performed using human umbilical vein endothelial cells (HUVECs). Results : The results showed that Glycyrrhiza uralensis extract exerted inhibitory effects on ONOO and ${\cdot}OH$. Tube formation in HUVEC was increase in a dose dependent manner. Conclusions : These results show the potential to promote the wound healing process by Glycyrrhiza uralensis extract.

• The Journal of Internal Korean Medicine
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• v.29 no.2
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• pp.490-499
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• 2008

Objectives : This study was aimed to elucidate the effects of Trichosanthes kirilowii extract (TKE) on the angiogenesis and growth of tumor cells. Methods : Tube formation assay was performed by using human umbilical vein endothelial cells (HUVEC), and anchorage dependent colony assay was performed by using B16-F10 melanoma, Hep G2 and HT1080, CT-26 and SNU-1 cells. Results : For HUVEC, TKE at a level of more than 100 ${\mu}g/m{\ell}$ suppresses cell growth. For HUVEC at 100 ${\mu}g/m{\ell}$ and greater TKE density, the formation of tubes was suppressed in a dose-dependant manner. TKE controls the colony formations of B16-F10 melanoma cells, CT 26 cells, and Hep G2 cells, and its effect is proportional to density. In HT1080 cells and SNU-1 cells, formation is suppressed regardless of density. Conclusions : From these results, it could be concluded that TKE has significant properties on anti-angiogenesis and growth inhibiting of tumor cells. It is suggested that TKE will be a good candidate for new drugs or therapeutics for anti-angiogenesis.

• Molecules and Cells
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• v.39 no.4
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• pp.292-298
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• 2016

Aquaporin 1 (AQP1) is expressed in most microvasculature endothelial cells and forms water channels that play major roles in a variety of physiologic processes. This study aimed to delineate the transcriptional regulation of AQP1 by Mef2c in endothelial cells. Mef2c cooperated with Sp1 to activate human AQP1 transcription by binding to its proximal promoter in human umbilical cord vein endothelial cells (HUVEC). Over-expression of Mef2c, Sp1, or Mef2c/Sp1 increased HUVEC migration and tube-forming ability, which can be abolished AQP1 knockdown. These data indicate that AQP1 is a direct target of Mef2c in regulating angiogenesis and vasculogenesis of endothelial cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.990-994
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• 2004

Cancer is an intractable disease for humans to overcome. Recently natural products or Oriental prescriptions have been on the spotlight to develop anticancer agents with little side-effects and good efficacy. KamikeKyuktang has been used for the treatment of cancer in Oriental medicine. However, its anti-cancer mechanism still remains unclear. KMKKTE is an ethanol extract of KamikeKyuktang composed of 12 medicinal herbs. Anti-proliferative effects of KMKKT was investigated on Lewis lung carcinoma cell (LLC) and A549 (human lung cancer cells). Half-maximal inhibition of the LLC and A549 cell proliferation by KMKKTE was found approximately 125㎍/㎖ and 250㎍/㎖, respectively. It also effectively inhibited the proliferation of HUVEC cells treated by bFGF and VEGF up to 30% of control at 125㎍/㎖ and the cell migration to 80% at 25 ㎍/㎖ in concentration dependent manner. Tube formation of HUVEC cells on matrigel also was significantly suppressed from 25㎍/㎖ of KMKKTE. Taken together, these results demonstrate that KMKKTE has antiangiogenic activity and be applied to angiogenesis dependent cancers.

• IMMUNE NETWORK
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• v.7 no.4
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• pp.203-208
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• 2007

Background: Angiogenesis mediated by VEGF constitutes a new target for anti-cancer therapy which has explored through different ways of intervention aiming at the blocking of the tumoral angiogenesis. In the present study, we developed the assays by which efficacies of anti-VEGF inhibitor candidates are evaluated at the various levels. Methods & Results: First, we developed two sandwich ELISAs using coated anti-VEGF Ab and soluble Flt-1 receptor fusion protein (sFlt-1/Fc). As low as 200 pg/ml of hVEGF diluted in human sera was detectable by these assays. In addition, we found that VEGF inhibitors ($2{\mu}g/ml$ of either anti-VEGF Ab or sFlt-1/Fc) completely block 5 ng/ml VEGF in these ELISAs. Subsequently, two bioassays, wound healing and HUVEC tube formation assays, revealed that anti-VEGF Ab $(1{\mu}g/ml)$ & sFlt-1/Fc Ab $(1{\mu}g/ml)$, or SU5416 (VEGFR tyrosine kinase inhibitor, $1{\mu}M$) prevents the activity of VEGF $(1{\sim}10ng/ml)$. Finally, secretion of MMP-9 by VEGF-stimulated macrophages was abolished by treatment of anti-VEGF Ab $(1{\mu}g/ml)$ in gelatin zymography. Conclusion: ELISAs together with bioassays developed in this study are appropriate for evaluation of the efficacy of inhibitors of VEGF.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.377-385
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• 2014

BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.397-401
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• 2001

In the search for new naturally occurring angiogenic inhibitory we found that culture broths from two unidentified fungal strains exerted potent inhibitory activities on capillary-like tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. Two active compounds were isolated by bioassay-guided separation and their structures were identified as gliotoxin (1) and its derivative methylthiogliotoxin (2) by spectroscopic analyses. These compounds significantly inhibited the migration of HUVEC assessed by in vitro wounding migration assay and exhibited at least 10 times more potent inhibition of proliferation of HUVECs as compared with that of cancer cell lines such as HeLa, MCF-7, and KB 3-1 cells. Especially, gliotoxin having disulfide group exerted more potent activities than methylthiogliotoxin, suggesting that gliotoxin could be a useful compound for further study as an anti-angiogenic agent.