TY - JOUR
T1 - Anti-angiogenic actions of the mangosteen polyphenolic xanthone derivative α-mangostin
AU - Jittiporn, Kanjana
AU - Suwanpradid, Jutamas
AU - Patel, Chintan
AU - Rojas, Modesto
AU - Thirawarapan, Suwan
AU - Moongkarndi, Primchanien
AU - Suvitayavat, Wisuda
AU - Caldwell, Ruth B.
N1 - Funding Information:
This research was completed in partial fulfillment of requirements for Dr. Jittiporn's PhD degree from Mahidol University in Bangkok, Thailand. The work was supported in part by The Ministry of Science and Technology, Thailand and the Department of Veterans Affairs , Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development (VA grant BX001233 ), the National Institutes of Health (NIH grant R01-EY11766 ) and the Culver Vision Discovery Institute ( BX001233 ) at Georgia Regents University. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors are grateful to Dr. Priya Narayanan, Ms. Zhimin Xu and Ms. Tahira Lemtalsi for advice and assistance in completion of the studies.
PY - 2014/5
Y1 - 2014/5
N2 - Retinal neovascularization is a major cause of vision loss in diseases characterized by retinal ischemia and is characterized by the pathological growth of abnormal vessels. Vascular endothelial growth factor (VEGF) is known to play an important role in this process. Oxidative stress has been strongly implicated in up-regulation of VEGF associated with neovascularization in various tissues. Hence, compounds with anti-oxidant actions can prevent neovascularization. α-Mangostin, a component of mangosteen (. Garcinia mangostana Linn), has been shown to have an anti-oxidant property in pathological conditions involving angiogenesis such as cancer. However, the effect of α-mangostin on ROS formation and angiogenic function in microvascular endothelial cells has not been studied. Hence, this study demonstrated the anti-angiogenic effects of α-mangostin in relation to ROS formation in bovine retinal endothelial cells (REC). α-Mangostin significantly and dose-dependently reduced formation of ROS in hypoxia-treated REC. α-Mangostin also significantly and dose-dependently suppressed VEGF-induced increases in permeability, proliferation, migration and tube formation in REC and blocked angiogenic sprouting in the ex vivo aortic ring assay. In addition, α-mangostin inhibited VEGF-induced phosphorylation of VEGFR2 and ERK1/2-MAPK. According to our results, α-mangostin reduces oxidative stress and limits VEGF-induced angiogenesis through a process involving abrogation of VEGFR2 and ERK1/2-MAPK activation.
AB - Retinal neovascularization is a major cause of vision loss in diseases characterized by retinal ischemia and is characterized by the pathological growth of abnormal vessels. Vascular endothelial growth factor (VEGF) is known to play an important role in this process. Oxidative stress has been strongly implicated in up-regulation of VEGF associated with neovascularization in various tissues. Hence, compounds with anti-oxidant actions can prevent neovascularization. α-Mangostin, a component of mangosteen (. Garcinia mangostana Linn), has been shown to have an anti-oxidant property in pathological conditions involving angiogenesis such as cancer. However, the effect of α-mangostin on ROS formation and angiogenic function in microvascular endothelial cells has not been studied. Hence, this study demonstrated the anti-angiogenic effects of α-mangostin in relation to ROS formation in bovine retinal endothelial cells (REC). α-Mangostin significantly and dose-dependently reduced formation of ROS in hypoxia-treated REC. α-Mangostin also significantly and dose-dependently suppressed VEGF-induced increases in permeability, proliferation, migration and tube formation in REC and blocked angiogenic sprouting in the ex vivo aortic ring assay. In addition, α-mangostin inhibited VEGF-induced phosphorylation of VEGFR2 and ERK1/2-MAPK. According to our results, α-mangostin reduces oxidative stress and limits VEGF-induced angiogenesis through a process involving abrogation of VEGFR2 and ERK1/2-MAPK activation.
UR - http://www.scopus.com/inward/record.url?scp=84901236284&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901236284&partnerID=8YFLogxK
U2 - 10.1016/j.mvr.2014.03.005
DO - 10.1016/j.mvr.2014.03.005
M3 - Article
C2 - 24721607
AN - SCOPUS:84901236284
SN - 0026-2862
VL - 93
SP - 72
EP - 79
JO - Microvascular Research
JF - Microvascular Research
ER -