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      ERK1/2 and HIF1 α Are Involved in Antiangiogenic Effect of Polyphenols-Enriched Fraction from Chilean Propolis

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          Abstract

          Propolis has been shown to modulate the angiogenesis in both in vitro and in vivo models. Thus, we aimed to evaluate the antiangiogenic properties of an ethanolic extract of Chilean propolis (EEP) and Pinocembrin (Pn). Migration, formation of capillary-like structures of endothelial cells, and sprouting from rat aortic rings were used to assess the antiangiogenic properties of EEP or Pn. In addition, microRNAs and VEGFA mRNA expression were studied by qPCR. ERK1/2 phosphorylation and HIF1 α stabilization were assessed by western blot. EEP or Pn attenuated the migration, the capillary-like tube formation, and the sprouting in the in vitro assays. In addition, the activation of HIF1 α and ERK1/2 and the VEGFA mRNA expression was significantly inhibited in a dose-dependent manner. In summary, these results suggest that HIF1 α and ERK1/2 phosphorylation could be involved in the antiangiogenic effect of Chilean propolis, but more studies are needed to corroborate these findings.

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          Most cited references34

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          TScratch: a novel and simple software tool for automated analysis of monolayer wound healing assays.

          Cell migration plays a major role in development, physiology, and disease, and is frequently evaluated in vitro by the monolayer wound healing assay. The assay analysis, however, is a time-consuming task that is often performed manually. In order to accelerate this analysis, we have developed TScratch, a new, freely available image analysis technique and associated software tool that uses the fast discrete curvelet transform to automate the measurement of the area occupied by cells in the images. This tool helps to significantly reduce the time needed for analysis and enables objective and reproducible quantification of assays. The software also offers a graphical user interface which allows easy inspection of analysis results and, if desired, manual modification of analysis parameters. The automated analysis was validated by comparing its results with manual-analysis results for a range of different cell lines. The comparisons demonstrate a close agreement for the vast majority of images that were examined and indicate that the present computational tool can reproduce statistically significant results in experiments with well-known cell migration inhibitors and enhancers.
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            The angiogenic switch in carcinogenesis.

            Coined in the late eighties, the term "angiogenic switch" refers to a time-restricted event during tumor progression where the balance between pro- and anti-angiogenic factors tilts towards a pro-angiogenic outcome, resulting in the transition from dormant avascularized hyperplasia to outgrowing vascularized tumor and eventually to malignant tumor progression. The molecular players and mechanisms underlying the angiogenic switch have been intensely investigated. In particular, a large number of pro-angiogenic factors and angiogenic inhibitors activated and repressed, respectively, in their activities during the angiogenic switch have been identified and characterized. Part of this research has lead to the development of various pro- and anti-angiogenic therapies that are currently tested in clinical trials or are already in clinical use. More recently, transgenic mouse models of cancer have been instrumental in revealing that inflammatory responses within the tumor microenvironment are critically contributing to the onset of tumor angiogenesis. These mouse models closely recapitulate multistage carcinogenesis in cancer patients and represent reliable tools to study the molecular and cellular players implicated in the onset and maintenance of tumor angiogenesis. Furthermore, they also offer the opportunity to assess the efficacy of novel anti-angiogenic cancer therapies and the nature of developing resistance mechanisms. These experiments have provided first important concepts to improve anti-angiogenic therapy and thus directly contribute to their translation to the clinical setting.
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              Propolis, an old remedy used in modern medicine.

              Propolis is one of the few natural remedies that has maintained its popularity over a long period of time. The pharmacologically active molecules in the propolis are flavonoids and phenolic acids and their esters. These components have multiple effects on bacteria, fungi and viruses. In addition, propolis and its components have anti-inflammatory and immunomodulatory activities. Moreover, propolis has been shown to lower blood pressure and cholesterol levels. However, clinical studies to substantiate these claims are required.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi Publishing Corporation
                1741-427X
                1741-4288
                2015
                10 August 2015
                10 August 2015
                : 2015
                : 187575
                Affiliations
                1Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Avenida Francisco Salazar 01145, 4781218 Temuco, Chile
                2Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, Avenida Professor Lineu Prestes 580, 05508-000 São Paulo, SP, Brazil
                3Departamento de Ciencias Preclínicas, Facultad de Medicina, Universidad de La Frontera, Claro Solar 115, 4781218 Temuco, Chile
                Author notes

                Academic Editor: Hyunsu Bae

                Article
                10.1155/2015/187575
                4546973
                bcd2a7b6-53d1-444a-83b5-5b2d988f4f23
                Copyright © 2015 Alejandro Cuevas et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 April 2015
                : 21 July 2015
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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