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Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo
Author(s) -
Isaji Masayuki,
Miyata Hiroshi,
Ajisawa Yoshiyuki,
Takehana Yasuo,
Yoshimura Nagahisa
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701493
Subject(s) - tranilast , angiogenesis , pharmacology , matrigel , in vivo , vascular endothelial growth factor , neovascularization , endothelium , angiogenesis inhibitor , endothelial stem cell , chemistry , medicine , in vitro , biology , endocrinology , cancer research , biochemistry , microbiology and biotechnology , vegf receptors
1 First developed as an antiallergic drug, tranilast inhibits chemical mediator release from mast cells. In the present study, we examine the effects of tranilast on angiogenesis in vitro and in vivo and discuss the application of tranilast for angiogenic diseases. 2 Tranilast inhibited significantly the proliferation (IC 50 : 136 μ M , 95% confidence limits: 124–137 μ M ) and vascular endothelium growth factor (VEGF)‐induced chemotaxis (IC 50 : 135 μ M , 95% confidence limits: 124–147 μ M ) of human dermal microvascular endothelial cells (HDMECs) at concentrations greater than 25 μg ml −1 . No toxicity to HDMECs measuring by LDH release and no inhibitory effects on metalloproteinase (MMP)‐2 and MMP‐9 activity were observed even at 100 μg ml −1 (306 μ M ). 3 Tube formation of HDMECs cultured on the matrigel as an in vitro angiogenesis model was inhibited by tranilast in a concentration‐dependent manner. The IC 50 value and 95% confidence limits were 175 μ M and 151–204 μ M , respectively. 4 In vivo angiogenesis was induced in mice by the subcutaneous injection of matrigel containing 30 ng ml −1 VEGF and 64 μg ml −1 heparin. Tranilast was administered orally twice a day for 3 days. Tranilast dose‐dependently suppressed angiogenesis in the matrigel and a significant change was observed at a dose of 300 mg kg −1 . 5 These results indicate that tranilast is an angiogenesis inhibitor which may be beneficial for the improvement of angiogenic diseases such as proliferative diabetic retinopathy, age‐related macular degeneration, tumour invasion and rheumatoid arthritis.British Journal of Pharmacology (1997) 122 , 1061–1066; doi: 10.1038/sj.bjp.0701493