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

Juni Ekowati, Suko Hardjono, Iwan Sahrial Hamid
Submission date: Tuesday, 01 December 2015
Published date: Sunday, 26 April 2015
DOI: http://dx.doi.org/10.18051/UnivMed.2015.v34.43-51

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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.

Keywords


Ethyl p-methoxycinnamate; chorio-allantoic membrane; angiogenesis; tyrosine kinase

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Universa Medicina by Faculty of Medicine, Trisakti University is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
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