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.

Ferulic Acid Prevents Angiogenesis Through Cyclooxygenase-2 and Vascular Endothelial Growth Factor in the Chick Embryo Chorioallantoic Membrane Model

“…In addition, we also collected the blood vessels of CAM in the formalin buffer and carried out microscopic observations of the histopathologic slide of the CAMusing Hematoxylin and Eosin (HE) staining. To confirm the antiangiogenic activity, this CAM assay was achieved with certain alteration as explained before 18,20 . The growth of the endothelial cell in the neovascular capillaries wasexposed in CAM cross-sections by an inverted phase contrast microscope, Nikon H600L.…”

“…Docking of FA molecule into each of the 3D structure of proteins was performed as described in our previous study 20 . The best docking results can be noticed by relating the structure of the docked FA molecule with the crystal structure of reference ligand in the binding site.…”

Determination of epms content and anti-inflammatory test rhizome extract Kaempferia galanga, L by inhibition of protein denaturation method

“…Umar et al (2012) reported that EPMC has a mechanism to inhibit COX1 and COX2. In the treatment of inflammation with kencur extract in the medical world, it was reported that kencur extract has the same effect as one of the non-steroidal anti-inflammatory drugs (NSAIDs) namely meloxicam (Ekowati et al, 2015 ;Syahruddin et al, 2017).…”

Pemodelan Molekul Turunan p-Metoksi sinnamoil Hidrazida Sebagai Inhibitor Checkpoint Kinase 1 dan Inhibitor Aromatase secara In silico

“…in vitro untuk aktivitas antiangiogenesis yang melibatkan hambatan enzim COX-2 berkolerasi linier dengan metode rat aortic ring assay (Umar et al, 2014), Chick Chorioallantoic Membrane (CAM) Assay (Ekowati et al, 2015;Hamid et al, 2013) dan Matrigel Assay (Donovan et al, 2001 (Meuth, 2010;Ruswanto, 2013;Putra et al, 2016). dan perkembangan sel kanker payudara (Suvannang et al, 2011;Dai et al, 2010;Winer at al., 2005;Wakeling at al., 2000).…”