Radicicol, a microbial cell differentiation modulator, inhibits in vivo angiogenesis.
Angiogenesis plays a significant role in various pathological states, including the progressive growth of solid tumors, rheumatoid arthritis, psoriasis, and diabetic retinopathy, in addition to its crucial role in embryonic development. Recent studies have revealed that an angiogenesis inhibitor is efficacious for these so-called angiogenic diseases. In the previous studies, we found that retinoids and vitamin D3 analogs, which are known to exhibit cell differentiation-modulating activity, effectively inhibit angiogenesis in vivo, thus forming the basis of our working hypothesis that a modulator of cell differentiation is capable of affecting angiogenesis. In this study, to verify this hypothesis further, radicicol (syn. monorden; 5-chloro-6-(7,8-epoxy-10-hydoxy-2-oxo-3,5-undecadienyl)-beta -resorcylic acid mu-lactone), a microbial cell differentiation modulator from a fungus, a strain of Neocosmospora tenuicristata, was examined for its anti-angiogenic activity in a bioassay system involving chorioallantoic membranes of growing chick embryos. The microbial cell differentiation modulator dose dependently inhibited embryonic angiogenesis, the ID50 value being 200 ng/egg. Radicicol also inhibited both the proliferation of and plasminogen activator production by vascular endothelial cells in the nM concentration range in a concentration-dependent manner, suggesting the possible involvement of these inhibitory effects in the anti-angiogenic action of the microbial product. These results indicate that radicicol might be a potential drug for treating different angiogenesis-dependent diseases, such as solid tumors, psoriasis, rheumatoid arthritis, and diabetic retinopathy.
Oikawa
T
T
Division of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
Ito
H
H
Ashino
H
H
Toi
M
M
Tominaga
T
T
Morita
I
I
Murota
S
S
D000482:Allantois / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D007783:Lactones / Q000494:pharmacology; D018942:Macrolides; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011145:Polyvinyls; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects
D007783:Lactones; D018942:Macrolides; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D014568:Urokinase-Type Plasminogen Activator; C035359:monorden