scholarly journals Anti-Angiogenic Effect of Asperchalasine A Via Attenuation of VEGF Signaling

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 358 ◽  
Author(s):  
Jun Yeon Park ◽  
Young Seok Ji ◽  
Hucheng Zhu ◽  
Yonghui Zhang ◽  
Do Hwi Park ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Chorioallantoic Membrane ◽  
Growth Factor Receptor ◽  
Tube Formation ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Concentration Dependent Manner ◽  
Endothelial Growth Factor

Cytochalasans are a group of structurally diverse fungal polyketide-amino acid hybrid metabolites that exhibit diverse biological functions. Asperchalasine A was identified and isolated from an extract of the marine-derived fungus, Aspergillus. Asperchalasine A is a cytochalasan dimer which consists of two cytochalasan molecules connected by an epicoccine. This study investigated the potential antiangiogenic effects of Aspergillus extract and asperchalasine A, which significantly inhibited cell adhesion and tube formation in human umbilical vein endothelial cells (HUVECs). Aspergillus extract and asperchalasine A decreased the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)-2 mRNA expression in a concentration-dependent manner. In addition, Aspergillus extract and asperchalasine A inhibited angiogenesis via downregulation of VEGF, p-p38, p-extracellular signal-regulated protein kinase (ERK), p-VEGFR-2, and p-Akt signaling pathways. Moreover, Aspergillus extract and asperchalasine A significantly inhibited the amount of blood vessel formation in fertilized chicken eggs using a chorioallantoic membrane assay. Our results provide experimental evidence of this novel biological activity of the potential antiangiogenic substances, Aspergillus extract, and asperchalasine A. This study also suggests that Aspergillus extract and its active component asperchalasine A are excellent candidates as adjuvant therapeutic substances for cancer prevention and treatment.

scholarly journals ATAD2 silencing decreases VEGFA secretion through targeting has-miR-520a to inhibit angiogenesis in colorectal cancer

2018 ◽  
Vol 96 (6) ◽  
pp. 761-768 ◽  
Author(s):  
Sen Hong ◽  
Si Chen ◽  
Xu Wang ◽  
Di Sun ◽  
Zhenkun Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Vascular Endothelial ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Growth Factor

ATPase family AAA domain-containing protein 2 (ATAD2) is involved in various types of cancers, including colorectal cancer. This study aimed to determine the role of ATAD2 in angiogenesis in colorectal cancer. Here, we downregulated ATAD2 expression in HCT116 and SW480 cells, and collected the conditioned medium (CM) from control and ATAD2-silenced cells. The effect of CM on human umbilical vein endothelial cells (HUVEC) was evaluated by using CCK-8, wound healing, tube formation, Western blot, and dual-luciferase reporter assays. Our results showed that the proliferation, migration, and tube formation of HUVEC were reduced in presence of ATAD2-silenced CM, and the levels of phosphorylated vascular endothelial growth factor receptor 2 (P-VEGFR2), CD31, and CD34 were downregulated. Mechanism studies showed that ATAD2 silencing regulated the expression of vascular endothelial growth factor A (VEGFA) and miR-520a. Moreover, we found that miR-520a could bind to ATAD2, and its inhibitor partly reversed the alterations in HUVEC induced by CM from ATAD2-silenced cells. In addition, we demonstrated that miR-520a directly bound to 3′-UTR of VEGFA and inhibited its expression. Collectively, our results indicate that ATAD2 inhibition suppresses VEGFA secretion by increasing miR-520a levels. Our study suggests ATAD2 as a potential therapeutic target for angiogenesis in colorectal cancer.

Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation

2015 ◽  
Vol 113 (02) ◽  
pp. 329-337 ◽  
Author(s):  
Peter W. Hewett ◽  
Takeshi Fujisawa ◽  
Samir Sissaoui ◽  
Meng Cai ◽  
Geraldine Gueron ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Carbon Monoxide ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Tube Formation ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Sprouting Angiogenesis ◽  
Endothelial Growth Factor

SummaryCarbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor-reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.

Glipizide Combined with ANP Suppresses Breast Cancer Growth and Metastasis by Inhibiting Angiogenesis through VEGF/VEGFR2 Signaling

2021 ◽  
Vol 21 ◽  
Author(s):  
Guanquan Mao ◽  
Shuting Zheng ◽  
Jinlian Li ◽  
Xiaohua Liu ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Natriuretic Peptide ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Cancer Growth ◽  
Vascular Endothelial ◽  
Breast Cancer Growth ◽  
Endothelial Growth Factor

Background: Breast cancer is one of the most common cancers worldwide among women, and angiogenesis has an important effect on its growth and metastasis. Glipizide, which is a widely used drug for type 2 diabetes mellitus, has been reported to inhibit tumor growth and metastasis by upregulating the expression of natriuretic peptide receptor A (NPRA). Atrial natriuretic peptide (ANP), the receptor of NPRA, plays an important role in angiogenesis. The purpose of this study was to explore the effect of glipizide combined with ANP on breast cancer growth and metastasis. Methods: To investigate the effect of glipizide combined with ANP on breast cancer, glipizide, ANP or glipizide combined with ANP was intraperitoneally injected into MMTV-PyMT mice. To explore whether the anticancer efficacy of glipizide combined with ANP was correlated with angiogenesis, a tube formation assay was performed. Results: Glipizide combined with ANP was found to inhibit breast cancer growth and metastasis in MMTV-PyMT mice, which spontaneously develop breast cancer. Furthermore, the inhibitory effect of ANP combined with glipizide was better than that of glipizide alone. ANP combined with glipizide significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) by suppressing vascular endothelial growth factor (VEGF)/VEGFR2 (vascular endothelial growth factor receptor 2) signaling. Conclusions: These results demonstrate that glipizide combined with ANP has a greater potential than glipizide alone to be repurposed as effective agents for the treatment of breast cancer by targeting tumor-induced angiogenesis.

scholarly journals Alkaloid extract of Corydalis yanhusuo inhibits angiogenesis via targeting vascular endothelial growth factor receptor signaling

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Wan ◽  
Yang Zhao ◽  
Qun Zhang ◽  
Guangyi Gao ◽  
Shanlan Zhang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Wide Spectrum ◽  
Growth Factor Receptor ◽  
Tube Formation ◽  
Drug Candidate ◽  
Vascular Endothelial ◽  
Migration Ability ◽  
Endothelial Growth Factor

Abstract Background Corydalis yanhusuo W.T. Wang (YHS) is a well-known Chinese flowering herbal plant commonly used for centuries in functional food and traditional Chinese medicine. In the present study, we have identified and characterized a novel inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) with low toxicity, alkaloid extract of YHS, which suppressed angiogenesis that plays a fundamental role in a wide spectrum of physiological functions and pathological processes. Methods Proliferative ability of human umbilical vascular endothelial cells (HUVECs) was assessed using MTT assay and Ki67 immunofluorescence staining. Migration ability of HUVECs was evaluated by wound healing and transwell assays. In vitro angiogenesis was tested by spheroid sprouting and tube formation assays. In vivo vascularization was examined using Matrigel plug and chick chorioallantoic membrane (CAM) models. Protein expression and phosphorylation levels of VEGFR2, AKT, ERK and STAT3 were determined by Western blot assay. Results We demonstrated that alkaloid extract of YHS significantly inhibited a variety of VEGF-induced angiogenesis processes including proliferation, migration, sprouting, and tube formation of HUVECs. Moreover, alkaloid extract of YHS contributed to reduced in vivo neo-vessel formation in Matrigel plugs of mice and CAM models. Further mechanistic studies revealed that alkaloid extract of YHS suppressed VEGF-induced signaling pathway as evaluated by diminished phosphorylation of VEGFR2 and subsequently attenuated its downstream regulators including phospho-ERK1/2, phospho-AKT and phospho-STAT3 levels in HUVECs. Conclusion Collectively, these preclinical findings indicate that alkaloid extract of YHS remarkably limits angiogenesis and may serve as a promising anti-angiogenic drug candidate.

Variable effects of alpha v suppression on VEGFR-2 expression in endothelial cells of different vascular beds

2009 ◽  
Vol 102 (11) ◽  
pp. 975-982 ◽  
Author(s):  
Tami Livnat ◽  
Uri Seligsohn ◽  
Rima Dardik
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Mobility Shift ◽  
Genetic Ablation ◽  
Vascular Beds ◽  
Endothelial Growth Factor

SummaryIntegrins αvβ3 and αvβ5 have been long considered as proangiogenic receptors, yet genetic ablation studies demonstrated enhanced angiogenesis in mice lacking αvβ3 and αvβ5 integrins, which was attributed to increased expression of vascular endothelial growth factor receptor-2 (VEGFR-2). In this study, we determined the effect of αvβ3 and αvβ5 suppression in endothelial cells (EC) on vascular endothelial growth factor (VEGF) and VEGFR-2 expression. αv was suppressed by shRNA in HUVEC (venous endothelial cells) and HMVEC (microvascular endothelial cells).VEGFR-2 was significantly upregulated by αv suppression in HUVEC and downregulated in HMVEC at both mRNA and protein levels,as assessed by real-time PCR and flow cytometry,respectively.HMVEC displayed completely abolished Sp1 binding to the VEGFR-2 promoter, and HUVEC exhibited enhanced binding to the –170 E- Box element in the VEGFR-2 promoter, assessed by electrophoretic mobility shift assay. Realtime PCR also revealed opposite effects on the expression of 5 additional important genes involved in angiogenesis in the two cell types.VEGF mRNA expression was enhanced in HUVEC and reduced in HMVEC; however, these alterations were not statistically significant.VEGF-induced proliferation was upregulated in HUVEC and reduced in HMVEC following αv suppression. No tube formation on Matrigel was observed in αv suppressed cells, regardless of their origin.These results indicate that suppression of αv integrins can either augment or inhibit VEGFR-2 levels and VEGF-induced proliferation in EC from different vascular beds. Hence, therapeutic antiangiogenic intervention by siRN-Amediated suppression of αv integrins should take into account variable and potentially hazardous responses in different vascular beds.

scholarly journals Regulation of vascular endothelial growth factor receptor 2 trafficking and angiogenesis by Golgi localized t-SNARE syntaxin 6

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1425-1435 ◽  
Author(s):  
Venkatraman Manickam ◽  
Ajit Tiwari ◽  
Jae-Joon Jung ◽  
Resham Bhattacharya ◽  
Apollina Goel ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Golgi Apparatus ◽  
Growth Factor Receptor ◽  
Brefeldin A ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Protein Receptor ◽  
Mouse Ear ◽  
Endothelial Growth Factor

Abstract Vascular endothelial growth factor receptor 2 (VEGFR2) plays a key role in physiologic and pathologic angiogenesis. Plasma membrane (PM) levels of VEGFR2 are regulated by endocytosis and secretory transport through the Golgi apparatus. To date, the mechanism whereby the VEGFR2 traffics through the Golgi apparatus remains incompletely characterized. We show in human endothelial cells that binding of VEGF to the cell surface localized VEGFR2 stimulates exit of intracellular VEGFR2 from the Golgi apparatus. Brefeldin A treatment reduced the level of surface VEGFR2, confirming that VEGFR2 traffics through the Golgi apparatus en route to the PM. Mechanistically, we show that inhibition of syntaxin 6, a Golgi-localized target membrane-soluble N-ethylmaleimide attachment protein receptor (t-SNARE) protein, interferes with VEGFR2 trafficking to the PM and facilitates lysosomal degradation of the VEGFR2. In cell culture, inhibition of syntaxin 6 also reduced VEGF-induced cell proliferation, cell migration, and vascular tube formation. Furthermore, in a mouse ear model of angiogenesis, an inhibitory form of syntaxin 6 reduced VEGF-induced neovascularization and permeability. Our data demonstrate the importance of syntaxin 6 in the maintenance of cellular VEGFR2 levels, and suggest that the inhibitory form of syntaxin 6 has good potential as an antiangiogenic agent.

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