Inhibition of the VEGFR-2 tyrosine kinase domain by witd Roman chamomile extracts and phenolic compounds
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resumo
Angiogenesis results from new blood vessels growing excessively (e. g. câncer). The Vascular
Endothelial Growth Factor (VEGF) is secreted by the tumor cells and plays a crucial role in
angiogenesis; low oxygen tension dramatically induces the expression of this major angiogenic
factor that when linked to the transmembrane tyrosine kinase receptor VEGFR-2, which is
present in endothelial cells, signalizes for the proliferation of these cells towards the tumor.
Treatments using small molecules with anti-tyrosine kinase activity (e. g., sorafenib) can block
angiogenic signalling, reduce blood tumoral irrigation, and improve chemotherapy distribution
[1]. Some studies recognized phenolic compounds as chemopreventive agents, especially
flavonoids. Other plant-derived anticancer drugs (e. g. Taxol) proved to be anti-angiogenic. In
traditional Chinese medicine, many herbs are used in the treatment of angiogenic diseases
such as chronic wounds and rheumatoid arthritis [2]. Furthermore, it has been reported that
drinking of green tea could inhibit VEGF-induced angiogenesis in vivo [3]. In the present work,
the anti-angiogenic activity of Roman chamomile (Chamaemelum nobile L.) extracts (methanolic
extract and infusion) and main phenolic compounds (apigenin, apigenin-7-O-glucoside, caffeic
acid, chlorogenic acid, luteolin, luteolin-7-O-glucoside) was evaluated through an enzymatic
assay using the VEGFR-2 tyrosine kinase domain. To better understand the inhibition
phosphorylation mechanism of the tyrosine kinase receptor by luteolin, apigenin and apigenin-7-
0-glucoside, docking studies were performed. The methanolic extract showed higher
phosphorylation inhibition than the infusion (IC50 values of 269 and 301 μg/mL, respectively).
Regarding phenolic compounds, luteolin (IC50 2.10 μM) and apigenin (IC50 4.78 μM) were the
most potent in inhibiting VEGFR-2 phosphorylation, leading us to believe that these compounds
are involved in the anti-angiogenic activity revealed by the methanolic extract.
