Red Raspberry Phenols Inhibit Angiogenesis: A Morphological and Subcellular Analysis Upon Human Endothelial Cells

Journal Article · Wed Mar 16 00:00:00 EDT 2016 · Journal of Cellular Biochemistry

DOI:https://doi.org/10.1002/jcb.25452· OSTI ID:1400529

Sousa, M. ^[1]; Machado, V. ^[1]; Costa, R. ^[1]; Figueira, M. E. ^[2]; Sepodes, B. ^[2]; Barata, P. ^[3]; Ribeiro, L. ^[4]; Soares, R. ^[1]

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1. Department of Biochemistry, Faculty of Medicine, Al Prof Hernâni Monteiro, 4200–319 Porto, I3S Instituto de Investigação e Inovação em Saúde Porto Portugal
2. Department of Pharmacology Faculty of Pharmacy University of Lisbon AV Prof Gama Pinto 1649‐003 Lisbon
3. Faculty of Health Sciences, University Fernando Pessoa, Pr Nove de abril, 4249‐004, Porto, Pharmacy Unit Central Hospital São João, Al Prof Hernâni Monteiro Pr Nove de abril 4200‐319 Porto
4. Department of Medical Education and Simulation, Faculty of Medicine, Al Prof Hernâni Monteiro, 4200‐319 Porto, I3S Instituto de Investigação e Inovação em Saúde Porto Portugal

ABSTRACT Polyphenols are a class of natural compounds whose potential as antioxidant, anti‐inflammatory, and anti‐angiogenesis has been reported in many pathological conditions. Red raspberry extract, rich in polyphenols, has been reported to exert anti‐inflammatory effects and prevent cell proliferation in distinct animal models. However, the signaling pathways involved remain unknown. Herein, we used human microvascular endothelial cells (HMVECs) to determine the influence of red raspberry phenolic compound extract concentrations, ranging from 10 to 250 µg gallic acid equivalents (GAE)/mL, on endothelium viability (MTS assay), proliferation (BrdU incorporation), migration (injury assay), and capillary‐like structures formation (Matrigel assay). Protein expression in cell lysates was determined by Western blot analysis. We showed that red raspberry extracts reduced cell viability (GI ₅₀  = 87,64 ± 6,59 μg GAE/mL) and proliferation in a dose‐dependent manner. A significant abrogation of cells ability to migrate to injured areas, even at low concentrations, was observed by injury assay. Cell assembly into capillary‐like structures on Matrigel also decreased in a dose dependent‐manner for higher extract concentrations, as well as the number of branching points per unit of area. Protein expression analysis showed a dose‐dependent decrease in Phospho‐VEGFR2 expression, implying abrogation of VEGF signaling activity. We also showed for the first time that red raspberry phenolic compounds induce the rearrangement of filamentous actin cytoskeleton, with an isotropy increase found for higher testing concentrations. Taken together, our findings corroborate the anti‐angiogenic potential of red raspberry phenolic compounds and provide new insights into their mode of action upon endothelium. J. Cell. Biochem. 117: 1604–1612, 2016. © 2015 Wiley Periodicals, Inc.

• Sponsoring Organization: USDOE
• OSTI ID: 1400529
• Journal Information: Journal of Cellular Biochemistry, Journal Name: Journal of Cellular Biochemistry Vol. 117 Journal Issue: 7; ISSN 0730-2312
• Publisher: Wiley Blackwell (John Wiley & Sons)
• Country of Publication: United States
• Language: English