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

Abstract

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