Ruta graveolens water extract inhibits cell-cell network formation in human umbilical endothelial cells via MEK-ERK1/2 pathway
| Autor: | Angela Chambery, Olga Pastorino, Rosita Russo, Federica Barbieri, Elisabeth Anne Illingworth, Michele Grieco, Luca Colucci-D'Amato, Sara Cioffi, Maria Teresa Gentile |
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| Přispěvatelé: | Gentile, Mariateresa, Russo, Rosita, Pastorino, Olga, Cioffi, Sara, Barbieri, Federica, Illingworth, Elisabeth Anne, Grieco, Michele, Chambery, Angela, Colucci-D'Amato, Luca |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Angiogenesis MAP Kinase Signaling System Endothelial cells Cell MAP Kinase Kinase 1 Biology Natural compound Natural compounds 03 medical and health sciences Endothelial cell Cell Movement medicine Human Umbilical Vein Endothelial Cells Humans Angiogenesis ERK signaling Endothelial cells Natural compounds RGWE VEGF Viability assay Cells Cultured Ruta Activator (genetics) Plant Extracts Water Cell Differentiation Cell Biology Transfection Nestin VEGF Cell biology Angiogenesi ERK signaling 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation RGWE Phosphorylation Signal transduction |
| Zdroj: | Experimental cell research 364 (2018): 50–58. doi:10.1016/j.yexcr.2018.01.025 info:cnr-pdr/source/autori:Gentile, Maria Teresa; Russo, Rosita; Pastorino, Olga; Cioffi, Sara; Barbieri, Federica; Illingworth, Elisabeth Anne; Grieco, Michele; Chambery, Angela; Colucci-D'Amato, Luca/titolo:Ruta graveolens water extract inhibits cell-cell network formation in human umbilical endothelial cells via MEK-ERK1%2F2 pathway/doi:10.1016%2Fj.yexcr.2018.01.025/rivista:Experimental cell research/anno:2018/pagina_da:50/pagina_a:58/intervallo_pagine:50–58/volume:364 |
| DOI: | 10.1016/j.yexcr.2018.01.025 |
| Popis: | Angiogenesis is a process encompassing several steps such as endothelial cells proliferation, differentiation and migration to form a vascular network, involving different signal transduction pathways. Among these, ERK1/2 signaling mediates VEGF-dependent signaling pathway. Here we report that the water extract of Ruta graveolens (RGWE), widely known as a medicinal plant, is able to impair in a dose-dependent manner, cell network formation without affecting cell viability. Biochemical analysis showed that the major component of RGWE is rutin, unable to reproduce RGWE effect. We found that RGWE inhibits ERK1/2 phosphorylation and that this event is crucial in cell network formation since the transfection of HUVEC with a constitutively active MEK (caMEK), the ERK1/2 activator, induces a robust cell network formation as compared to untransfected and/or mock transfected cells and, more importantly, caMEK transfected cells became unresponsive to RGWE. Moreover, RGWE inhibits VEGF and nestin gene expression, necessary for vessel formation, and the caMEK transfection induces their higher expression. In conclusion, we report that RGWE is able to significantly impair vessels network formation without affecting cell viability, preventing ERK1/2 activation and, in turn, down-regulating VEGF and nestin expression. These findings point to RGWE as a potential therapeutic tool capable to interfere with pathologic angiogenesis. Angiogenesis is a process encompassing several steps such as endothelial cells proliferation, differentiation and migration to form a vascular network, involving different signal transduction pathways. Among these, ERK1/2 signaling mediates VEGF-dependent signaling pathway. Here we report that the water extract of Ruta graveolens (RGWE), widely known as a medicinal plant, is able to impair in a dose-dependent manner, cell network formation without affecting cell viability. Biochemical analysis showed that the major component of RGWE is rutin, unable to reproduce RGWE effect. We found that RGWE inhibits ERK1/2 phosphorylation and that this event is crucial in cell network formation since the transfection of HUVEC with a constitutively active MEK (caMEK), the ERK1/2 activator, induces a robust cell network formation as compared to untransfected and/or mock transfected cells and, more importantly, caMEK transfected cells became unresponsive to RGWE. Moreover, RGWE inhibits VEGF and nestin gene expression, necessary for vessel formation, and the caMEK transfection induces their higher expression. In conclusion, we report that RGWE is able to significantly impair vessels network formation without affecting cell viability, preventing ERK1/2 activation and, in turn, down-regulating VEGF and nestin expression. These findings point to RGWE as a potential therapeutic tool capable to interfere with pathologic angiogenesis. |
| Databáze: | OpenAIRE |
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