Hindawi Publishing Corporation
International Journal of Vascular Medicine
Volume 2013, Article ID 843897, 8 pages
http://dx.doi.org/10.1155/2013/843897
Research Article
Inhibition of Angiogenesis In Vitro by Chebulagic Acid:
A COX-LOX Dual Inhibitor
A. P. Athira,
1
A. Helen,
1
K. Saja,
1
P. Reddanna,
2,3
and P. R. Sudhakaran
1,4
1
Department of Biochemistry, University of Kerala, hiruvananthapuram, Kerala 695581, India
2
National Institute of Animal Biotechnology, University of Hyderabad Campus, Hyderabad 500046, India
3
Department of Animal Sciences, University of Hyderabad, Hyderabad 500046, India
4
Department of Computational Biology and Bioinformatics, State Inter-University Centre for Excellence in Bioinformatics,
University of Kerala, hiruvananthapuram, Kerala 695581, India
Correspondence should be addressed to P. R. Sudhakaran; prslab@gmail.com
Received 30 April 2013; Accepted 13 September 2013
Academic Editor: Karlheinz Peter
Copyright © 2013 A. P. Athira et al. his is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Angiogenesis is a crucial step in the growth of cancer and its metastasis. It is regulated by several endogenous factors which may
stimulate or inhibit the new blood vessel growth. Besides these endogenous factors, several exogenous factors including some
natural compounds are known to modulate angiogenesis. Angiogenesis being a potential target for drugs against a number of
pathological conditions, search for compounds from natural sources that can afect angiogenesis is of great interest. he objective
of our present study was to understand the efect of chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia
chebula Retz., on angiogenesis. he model systems used were rat aortic rings and human umbilical vein endothelial cells. he results
showed that chebulagic acid exerts an antiangiogenic efect. his was evidenced from decreased sprouting in rat aortic rings and
decrease in biochemical markers in endothelial cells treated with chebulagic acid. It downregulated the production of CD31, E-
selectin, and vascular endothelial growth factor in human umbilical vein endothelial cells in culture (HUVEC). Further studies to
understand the molecular mechanism of action of chebulagic acid revealed that CA exerts its anti angiogenic efect by modulating
VE cadherin- catenin signalling in human umbilical vein endothelial cells.
1. Introduction
Angiogenesis, the regulated formation of new blood vessels
from preexisting ones, plays a crucial role in organogene-
sis, advanced embryonic development, wound healing, and
growth and action of female reproductive organs. Although
angiogenesis is essential during these processes, in adulthood,
it has a limited role in normal physiology and is mostly linked
to pathological conditions such as tumorigenesis, rheumatoid
arthritis, obesity, and diabetic retinopathy [1].
Angiogenesis is a complex and orderly process that
involves cell-cell and cell-extracellular matrix interactions,
which is controlled by a balance between angiogenic and
angiostatic factors. Disruption of this balance leads to aber-
rant angiogenesis resulting in pathological conditions, arising
due to hypo- or hyperangiogenesis [2]. he activation of
endothelial cells, the initial step of angiogenesis, occurs when
positive regulators predominate. he endothelial quiescence
is achieved and maintained by the dominance of negative
regulators [3, 4].
Apart from these endogenous factors, several exoge-
nous factors are known to modulate angiogenesis. Natu-
rally occurring bioactive compounds are gaining attention
as therapeutic agents since they modulate biological pro-
cesses that underlie many disease states. Angiogenesis being
a potential target for drugs against a number of pathological
conditions, search for compounds from natural sources that
can afect angiogenesis is of great interest. Much of the
recent research is focused on therapeutic approach to identify
natural compounds which are able to modulate angiogenesis.
Inhibition of angiogenesis is now considered to be one of the
most promising strategies leading to the development of new
antineoplastic therapies.