%0 Journal Article
%T Inhibition of Angiogenesis In Vitro by Chebulagic Acid: A COX-LOX Dual Inhibitor
%A A. P. Athira
%A A. Helen
%A K. Saja
%A P. Reddanna
%A P. R. Sudhakaran
%J International Journal of Vascular Medicine
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/843897
%X 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 affect angiogenesis is of great interest. The objective of our present study was to understand the effect of chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., on angiogenesis. The model systems used were rat aortic rings and human umbilical vein endothelial cells. The results showed that chebulagic acid exerts an antiangiogenic effect. This 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 effect 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 organogenesis, 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 aberrant angiogenesis resulting in pathological conditions, arising due to hypo- or hyperangiogenesis [2]. The activation of endothelial cells, the initial step of angiogenesis, occurs when positive regulators predominate. The endothelial quiescence is achieved and maintained by the dominance of negative regulators [3, 4]. Apart from these endogenous factors, several exogenous factors are known to modulate angiogenesis. Naturally occurring bioactive compounds are gaining attention as therapeutic agents since they
%U http://www.hindawi.com/journals/ijvm/2013/843897/