Iejimalides show anti-osteoclast activity via V-ATPase inhibition

Sayaka Kazami, Makoto Muroi, Makoto Kawatani, Takaaki Kubota, Takeo Usui, Jun'ichi Kobayashi, Hiroyuki Osada

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Iejimalides (IEJLs), 24-membered macrolides, are potent antitumor compounds, but their molecular targets remain to be revealed. In the course of screening, we identified IEJLs as potent osteoclast inhibitors. Since it is known that osteoclasts are sensitive to vacuolar H+-ATPase (V-ATPase) inhibitor, we investigated the effect of IEJLs on V-ATPases. IEJLs inhibited the V-ATPases of both mammalian and yeast cells in situ, and of yeast V-ATPases in vitro. A bafilomycin-resistant yeast mutant conferred IEJL resistance, suggesting that IEJLs bind a site similar to the bafilomycins/concanamycins- binding site. These results indicate that IEJLs are novel V-ATPase inhibitors, and that antitumor and antiosteporotic activities are exerted via V-ATPase inhibition.

Original languageEnglish
Pages (from-to)1364-1370
Number of pages7
JournalBioscience, Biotechnology and Biochemistry
Volume70
Issue number6
DOIs
Publication statusPublished - 2006
Externally publishedYes

Keywords

  • Antiosteoporotic
  • Antitumor
  • Bafilomycin
  • Iejimalide
  • V-ATPase

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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