Anti-angiogenic actions of the mangosteen polyphenolic xanthone derivative α-mangostin.
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.
Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA; Vascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA; Department of Physiology, Faculty of Pharmacy, Mahidol University, 10400, Thailand.
Kanjana
K
Jittiporn
Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA; Vascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA.
Jutamas
J
Suwanpradid
Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA; Vascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA.
Chintan
C
Patel
Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA; Vascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA.
Modesto
M
Rojas
Department of Physiology, Faculty of Pharmacy, Mahidol University, 10400, Thailand.
Suwan
S
Thirawarapan
Department of Microbiology, Faculty of Pharmacy, Mahidol University, 10400, Thailand.
Primchanien
P
Moongkarndi
Department of Physiology, Faculty of Pharmacy, Mahidol University, 10400, Thailand.
Wisuda
W
Suvitayavat
Vision Discovery Institute, Georgia Regents University, Augusta, GA 30912, USA; Vascular Biology Center, Georgia Regents University, Augusta, GA 30912, USA; VA Medical Center, Augusta, GA 30912, USA. Electronic address: rcaldwel@gru.edu.
Ruth B
RB
Caldwell
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D046509:Tissue Culture Techniques; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D044004:Xanthones; D040301:Vascular Endothelial Growth Factor Receptor-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C021053:mangostin