scholarly journals BA-12 Inhibits Angiogenesis via Glutathione Metabolism Activation

2019 ◽  
Vol 20 (16) ◽  
pp. 4062 ◽  
Author(s):  
Herong Cui ◽  
Wenbo Guo ◽  
Beibei Zhang ◽  
Guoping Li ◽  
Tong Li ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Low Cost ◽  
Chorioallantoic Membrane ◽  
Target Prediction ◽  
Carcinoma Cells ◽  
Glutathione Metabolism ◽  
Prunella Vulgaris ◽  
Antitumor Activities ◽  
Chick Chorioallantoic Membrane ◽  
Umbilical Vein Endothelial Cells

There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulae and pharmacochemistry, using a ligustrazine–betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional Prunella vulgaris plaster, BA-12 was synthesized according to our previous study, as it exhibited better antitumor activities than other derivatives on human bladder carcinoma cells (T24); it was then uploaded for target prediction. Secondly, the efficacy and biotoxicity of BA-12 on angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs), a quail chick chorioallantoic membrane, and Caenorhabditis elegans. According to the prediction results, the main mechanisms of BA-12 were metabolic pathways. Thus, multiple metabolomics approaches were applied to reveal the mechanisms of BA-12. Finally, the predictive mechanisms of BA-12 on glutathione metabolism and glycerophospholipid metabolism activation were validated using targeted metabolomics and pharmacological assays. This strategy may provide a reference for highly efficient drug discovery, with the aim of sharing TCM wisdom for unmet clinical needs.

scholarly journals Apigenin Suppresses Angiogenesis by Inhibiting Tube Formation and Inducing Apoptosis

2016 ◽  
Vol 11 (10) ◽  
pp. 1934578X1601101
Author(s):  
Hyun Ju Kim ◽  
Mok-Ryeon Ahn
Keyword(s):  
Umbilical Vein ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
Anticancer Activities ◽  
Apoptotic Pathway ◽  
Inhibition Of Angiogenesis ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells

Apigenin has been reported to exert angiogenic and anticancer activities in vitro. The mechanism of inhibition of angiogenesis by apigenin, however, has not been well-established. In this study, we investigated whether apigenin not only inhibited tube formation but also induced apoptosis in human umbilical vein endothelial cells (HUVECs). Furthermore, strong antiangiogenic activity of apigenin was observed in the in vivo assay using chick embryo chorioallantoic membrane (CAM). We also analyzed changes in survival signals and the apoptotic pathway through Western blotting. The results indicate that apigenin exerts its antiangiogenic effects through induction of endothelial apoptosis.

scholarly journals Secretome of Senescent Adipose-Derived Mesenchymal Stem Cells Negatively Regulates Angiogenesis

2020 ◽  
Vol 21 (5) ◽  
pp. 1802 ◽  
Author(s):  
Andrey Ratushnyy ◽  
Mariia Ezdakova ◽  
Ludmila Buravkova
Keyword(s):  
Replicative Senescence ◽  
Umbilical Vein ◽  
Chorioallantoic Membrane ◽  
Dot Blot ◽  
In Ovo ◽  
Angiogenic Potential ◽  
Associated Proteins ◽  
Migration Capacity ◽  
Umbilical Vein Endothelial Cells

Nowadays, paracrine regulation is considered as a major tool of mesenchymal stem cell (MSC) involvement in tissue repair and renewal in adults. Aging results in alteration of tissue homeostasis including neovascularization. In this study, we examined the influence of replicative senescence on the angiogenic potential of adipose-derived MSCs (ASCs). Angiogenic activity of conditioned medium (CM) from senescent and “young” ASCs was evaluated in chorioallantoic membrane (CAM) assay in ovo using Japanese quail embryos. Also, the formation of capillary-like tubes by human umbilical vein endothelial cells (HUVECs) in 3D basement membrane matrix “Matrigel” and HUVEC migration capacity were analyzed. Multiplex, dot-blot and gene expression analysis were performed to characterize transcription and production of about 100 angiogenesis-associated proteins. The results point to decreased angiogenic potential of senescent ASC secretome in ovo. A number of angiogenesis-associated proteins demonstrated elevation in CM after long-term cultivation. Meanwhile, VEGF (key positive regulator of angiogenesis) did not change transcription level and concentration in CM. Increasing both pro- (FGF-2, uPA, IL-6, IL-8 etc.) and antiangiogenic (IL-4, IP-10, PF4, Activin A, DPPIV etc.) factors was observed. Some proangiogenic genes were downregulated (IGF1, MMP1, TGFB3, PDGFRB, PGF). Senescence-associated secretory phenotype (SASP) modifications after long-term cultivation lead to attenuation of angiogenic potential of ASC.

scholarly journals A novel method of screening combinations of angiostatics identifies bevacizumab and temsirolimus as synergistic inhibitors of glioma-induced angiogenesis

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252233
Author(s):  
Michael I. Dorrell ◽  
Heidi R. Kast-Woelbern ◽  
Ryan T. Botts ◽  
Stephen A. Bravo ◽  
Jacob R. Tremblay ◽  
...  
Keyword(s):  
Side Effects ◽  
Tumor Angiogenesis ◽  
Clinical Success ◽  
Low Cost ◽  
Chorioallantoic Membrane ◽  
Cellular Interactions ◽  
Compensatory Mechanisms ◽  
Chick Chorioallantoic Membrane

Tumor angiogenesis is critical for the growth and progression of cancer. As such, angiostasis is a treatment modality for cancer with potential utility for multiple types of cancer and fewer side effects. However, clinical success of angiostatic monotherapies has been moderate, at best, causing angiostatic treatments to lose their early luster. Previous studies demonstrated compensatory mechanisms that drive tumor vascularization despite the use of angiostatic monotherapies, as well as the potential for combination angiostatic therapies to overcome these compensatory mechanisms. We screened clinically approved angiostatics to identify specific combinations that confer potent inhibition of tumor-induced angiogenesis. We used a novel modification of the ex ovo chick chorioallantoic membrane (CAM) model that combined confocal and automated analyses to quantify tumor angiogenesis induced by glioblastoma tumor onplants. This model is advantageous due to its low cost and moderate throughput capabilities, while maintaining complex in vivo cellular interactions that are difficult to replicate in vitro. After screening multiple combinations, we determined that glioblastoma-induced angiogenesis was significantly reduced using a combination of bevacizumab (Avastin®) and temsirolimus (Torisel®) at doses below those where neither monotherapy demonstrated activity. These preliminary results were verified extensively, with this combination therapy effective even at concentrations further reduced 10-fold with a CI value of 2.42E-5, demonstrating high levels of synergy. Thus, combining bevacizumab and temsirolimus has great potential to increase the efficacy of angiostatic therapy and lower required dosing for improved clinical success and reduced side effects in glioblastoma patients.

scholarly journals Use of costic acid, a natural extract fromDittrichia viscosa, for the control ofVarroa destructor, a parasite of the European honey bee

2017 ◽  
Vol 13 ◽  
pp. 952-959 ◽  
Author(s):  
Kalliopi Sofou ◽  
Demosthenis Isaakidis ◽  
Apostolos Spyros ◽  
Anita Büttner ◽  
Athanassios Giannis ◽  
...  
Keyword(s):  
Honey Bee ◽  
Varroa Destructor ◽  
Umbilical Vein ◽  
Low Cost ◽  
Acaricidal Activity ◽  
Natural Extract ◽  
Dittrichia Viscosa ◽  
Umbilical Vein Endothelial Cells ◽  
Bee Colonies

Costic acid has been isolated from the plantDittrichia viscosaand its efficacy againstVarroa destructor, a parasite ofApis mellifera, the European honey bee, has been studied. Costic acid exhibited potent in vivo acaricidal activity against the parasite. Initial experiments showed that the compound is not toxic for human umbilical vein endothelial cells (HUVEC) at concentrations of up to 230 micromolar (μM), indicating that costic acid could be used as a safe, low-cost and efficient agent for controlling varroosis in honey bee colonies.

scholarly journals Cellular Metabolomics Reveal the Mechanism Underlying the Anti-Atherosclerotic Effects of Aspirin Eugenol Ester on Vascular Endothelial Dysfunction

2019 ◽  
Vol 20 (13) ◽  
pp. 3165 ◽  
Author(s):  
Mei-Zhou Huang ◽  
Xiao-Rong Lu ◽  
Ya-Jun Yang ◽  
Xi-Wang Liu ◽  
Zhe Qin ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Glutathione Metabolism ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Induced Apoptosis ◽  
Umbilical Vein Endothelial Cells ◽  
Oxidative Effects ◽  
Aspirin Eugenol Ester

Aspirin eugenol ester (AEE) possesses anti-thrombotic, anti-atherosclerotic and anti-oxidative effects. The study aims to clarify the mechanism underlying the anti-atherosclerotic effects of AEE on vascular endothelial dysfunction. Both the high-fat diet (HFD)-induced atherosclerotic rat model and the H2O2-induced human umbilical vein endothelial cells (HUVECs) model were used to investigate the effects of AEE on vascular endothelial dysfunction. UPLC/QTOF-MS coupled with a multivariate data analysis method were used to profile the variations in the metabolites of HUVECs in response to different treatments. Pretreatment of HUVECs with AEE significantly ameliorated H2O2-induced apoptosis, the overexpression of E-selectin and VCAM-1, and the adhesion of THP-1 cells. Putative endogenous biomarkers associated with the inhibition of endothelial dysfunction were identified in HUVECs pretreated with AEE in the absence or presence of H2O2, and these biomarkers were involved in important metabolic pathways, including amino acid metabolism, carbohydrate metabolism, and glutathione metabolism. Moreover, in vivo, AEE also significantly reduced vascular endothelial dysfunction and decreased the overexpression of VCAM-1 and E-selectin. Based on our findings, the mechanism underlying the anti-atherosclerotic effects of AEE might be related to a reduction in vascular endothelial dysfunction mediated by ameliorating alterations in metabolism, inhibiting oxidative stress, and decreasing the expression of adhesion molecules.

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