Clotrimazole, an imidazole antimycotic, is a potent inhibitor of angiogenesis

Hiroto Takahashi, Mayumi Abe, Toshiyuki Sugawara, Katsuhiro Tanaka, Yasuki Saito, Sigefumi Fujimura, Masabumi Shibuya, Yasufumi Sato

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 μM 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 I 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.

Original languageEnglish
Pages (from-to)445-451
Number of pages7
JournalJapanese Journal of Cancer Research
Volume89
Issue number4
DOIs
Publication statusPublished - 1998 Apr

Keywords

  • Angiogenesis
  • Angiogenesis inhibition
  • Basic fibroblast growth factor
  • Clotrimazole
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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