Ferulago angulata flower and leaf extracts inhibit angiogenesis in vitro through reducing VEGF-A and VEGFR-2 genes expression.
BACKGROUND
Ferulago angulata (Apiacea) has been used in Iranian traditional medicine since ancient times and its various health care and pharmacological benefits have been demonstrated recently. In this study, for the first time, we have investigated the effects of F. angulata flower and leaf ethanol extracts on angiogenesis, as the key process in tumor growth, invasion and metastasis.


METHODS
Cytotoxic effects of different concentrations (20-140 µg/mL) of each extract were assessed on human umbilical vein endothelial cells (HUVECs) using neutral red uptake assay. After evaluating the less toxic concentrations (up to 80 µg/mL), we performed three-dimensional angiogenesis, tube formation and migration assays to assess the key properties of HUVECs, including the angiogenesis process, in response to the extracts. Finally, quantitative gene expression analysis of VEGF-A and VEGFR-2, two critical mediators of angiogenesis, was performed using real-time RT-PCR.


RESULTS
Both flower and leaf extracts exhibited concentration-dependent inhibition of sprouting, tube formation and migration capacities of HUVECs. For the flower extract, the respective IC50 values were 25.79, 26.52 and 38.92 µg/mL while for the leaf extract, the corresponding IC50 values were 34.18, 41.24 and 28.69 µg/mL. Both flower and leaf extracts downregulated VEGF-A and VEGFR-2 genes relative to the GAPDH gene as the internal control at concentrations of 60 and 80 µg/mL, respectively.


CONCLUSIONS
These findings suggest that both flower and leaf extracts may contain anti-angiogenic compounds and may have the capacity to be utilized in tumor anti-angiogenic therapy strategies.
Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.hassan_akrami@yahoo.com.
Somaye
S
Mirzaaghaei
Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.
Hassan
H
Akrami
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Kamran
K
Mansouri
D019661:Apiaceae; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D035264:Flowers; D015870:Gene Expression / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2