CLOTRIMAZOLE, AN IMIDAZOLE ANTIMYCOTIC, IS A POTENT INHIBITOR OF ANGIOGENESIS

Clotrimazole, an imidazole antimycotic, interferes with the rise in cy tosolic Ca2+ and inhibits cell proliferation in a reversible manner. H ere we describe the effect of clotrimazole on vascular endothelial cel ls (ECs). Clotrimazole inhibited the proliferation of ECs stimulated w ith typical angiogenic growth factors; vascular endothelial growth fac tor and basic fibroblast growth factor (bFGF). This inhibitory effect of clotrimazole was dose-dependent and the maximal inhibition was obse rved at a concentration of 10 mM. We did not observe any increase in C r-51 release from ECs during treatment,vith 10 mu M clotrimazole. More over, clotrimazole inhibited the basal and bFGF-stimulated migration o f ECs. As clotrimazole inhibited two principle components of angiogene sis; the proliferation and migration of ECs, we examined whether clotr imazole inhibited angiogenesis. Tube formation by ECs in type 1 collag en gel was investigated, and clotrimazole was found to be significantl y inhibitory. The inhibitory effect of clotrimazole on angiogenesis wa s further confirmed in an in vivo angiogenesis model of murine Matrige l plug assay. These results demonstrate that clotrimazole is a potent inhibitor of angiogenesis.