Anti-angiogenic effects of Shiraiachrome A, a compound isolated from a Chinese folk medicine used to treat rheumatoid arthritis.
The Chinese folk medicine Shiraia bambusicola has long been utilized in the treatment of rheumatoid arthritis, a disease in which angiogenesis plays an important role. We report here the isolation of the compound Shiraiachrome A from S. bambusicola and the demonstration of its anti-angiogenic properties. We found that Shiraiachrome A significantly inhibited the proliferation, migration, and tube formation of human microvascular endothelial cells (HMEC) in a dose-dependent manner, with average IC(50) values of 2.1+/-0.36, 1.97+/-0.44, and 1.65+/-0.59 microM, respectively. In addition, Shiraiachrome A inhibited the formation of new microvessels in a rat aorta culture model as well as in the chick embryo chorioallantoic membrane (CAM) assay. Investigation of the mechanism of action of Shiraiachrome A demonstrated that this compound suppressed the autophosphorylation of four receptor tyrosine kinases (RTKs), with IC(50) values ranging from 2.2 to 4.3 microM. These results suggest that Shiraiachrome A inhibits angiogenesis by blocking growth factor-stimulated autophosphorylation of RTKs. These findings also indicate that Shiraiachrome A may be a potent therapeutic agent for angiogenesis-related diseases such as cancer, rheumatoid arthritis, and diabetic retinopathy.
Tong
Yunguang
Y
Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, 555 Zu-chong-zhi Road, Shanghai 201203, PR China.
Zhang
Xiongwen
X
Zhao
Weimin
W
Zhang
Yixiang
Y
Lang
Jingyu
J
Shi
Yuhua
Y
Tan
Wenfu
W
Li
Meihong
M
Zhang
Yongwei
Y
Tong
Linjiang
L
Lu
He
H
Lin
Liping
L
Ding
Jian
J
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002196:Capillaries / Q000187:drug effects / Q000648:ultrastructure; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects; D015151:Immunoblotting; D007202:Indicators and Reagents; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D041681:NIH 3T3 Cells; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D007202:Indicators and Reagents; C075921:Shiraiachrome A; D010569:Perylene; D020794:Receptor Protein-Tyrosine Kinases