Clotrimazole, an imidazole antimycotic, is a potent inhibitor of angiogenesis.
Clotrimazole, an imidazole antimycotic, interferes with the rise in cytosolic Ca2+ and inhibits cell proliferation in a reversible manner. Here we describe the effect of clotrimazole on vascular endothelial cells (ECs). Clotrimazole inhibited the proliferation of ECs stimulated with typical angiogenic growth factors; vascular endothelial growth factor and basic fibroblast growth factor (bFGF). This inhibitory effect of clotrimazole was dose-dependent and the maximal inhibition was observed at a concentration of 10 mM. We did not observe any increase in 51Cr release from ECs during treatment with 10 microM clotrimazole. Moreover, clotrimazole inhibited the basal and bFGF-stimulated migration of ECs. As clotrimazole inhibited two principle components of angiogenesis; the proliferation and migration of ECs, we examined whether clotrimazole inhibited angiogenesis. Tube formation by ECs in type 1 collagen gel was investigated, and clotrimazole was found to be significantly inhibitory. The inhibitory effect of clotrimazole on angiogenesis was further confirmed in an in vivo angiogenesis model of murine Matrigel plug assay. These results demonstrate that clotrimazole is a potent inhibitor of angiogenesis.
Takahashi
H
H
Department of Vascular Biology, Tohoku University, Sendai.
Abe
M
M
Sugawara
T
T
Tanaka
K
K
Saito
Y
Y
Fujimura
S
S
Shibuya
M
M
Sato
Y
Y
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001672:Biocompatible Materials; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003022:Clotrimazole / Q000494:pharmacology*; D003094:Collagen / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000502:physiology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011509:Proteoglycans / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000935:Antifungal Agents; D001672:Biocompatible Materials; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D007797:Laminin; D008222:Lymphokines; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen; D003022:Clotrimazole