Ethyl p-methoxycinnamate from Kaempferia galanga inhibits angiogenesis through tyrosine kinase

Abstract

BACKGROUND<br />Many tumors express on their receptor tyrosine kinases vascular endothelial<br />growth factor activity associated with angiogenesis. Inhibition of<br />angiogenesis through reduction of tyrosine kinase activity is a promising<br />strategy for cancer therapy. The present study aimed to determine the<br />mechanism and potency of ethyl p-methoxycinnamate (EPMC) isolated<br />from Kaempferia galanga as angiogenesis inhibitor.<br />METHODS<br />A laboratory experimental study was conducted using chorio-allantoic<br />membranes (CAMs) of nine-day old chicken eggs induced by 60ng basic<br />fibroblast growth factor (bFGF). Ethyl p-methoxycinnamate (EPMC) potency<br />was determined at dosages of 30, 60, 90 and 120 μg and compared with<br />celecoxib 60 μg as reference drug and one negative bFGF-induced control<br />group. Neovascularization and endothelial cell count in CAM blood vessels<br />were evaluated. To predict the antiangiogenic mechanism of EPMC, a<br />docking study was performed with the Molegro Virtual Docker program on<br />tyrosine kinase as receptor (PDB 1XKK).<br />RESULTS<br />Angiogenesis stimulation by bFGF was prevented significantly (p<0.05)<br />by EPMC at dosages of 30, 60, 90 and 120 μg and this activity was dose<br />dependent. Molecular docking showed interaction between EPMC functional<br />groups and tyrosine kinase amino acids at Met766, Met793, Thr854, Thr790,<br />Gln791 and Ala743. There was an association between EPMC<br />antiangiogenic activity and docking study results.<br />CONCLUSIONS<br />Ethyl p-methoxycinnamate is a potential new angiogenesis inhibitor through<br />interaction with tyrosine kinase. EPMC could be a promising therapeutic<br />agent for treatment of angiogenesis-related diseases.