Glaziovianin A Prevents Endosome Maturation via Inhibiting Microtubule Dynamics

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• 作者：Takumi Chinen ; Sayaka Kazami ; Yoko Nagumo ; Ichiro Hayakawa ; Akiyuki Ikedo ; Masatoshi Takagi ; Akihito Yokosuka ; Naoko Imamoto ; Yoshihiro Mimaki ; Hideo Kigoshi ; Hiroyuki Osada ; Takeo Usui
• 刊名：ACS Chemical Biology
• 出版年：2013
• 出版时间：May 17, 2013
• 年：2013
• 卷：8
• 期：5
• 页码：884-889
• 全文大小：350K
• 年卷期：v.8,no.5(May 17, 2013)
• ISSN：1554-8937

文摘

Glaziovianin A, an isoflavone isolated from the leaves of Ateleia glazioviana, inhibits the cell cycle progression in M-phase with an abnormal spindle structure, but its inhibitory mechanism has not been revealed. Here, we report that glaziovianin A and its derivatives are microtubule dynamics inhibitors. Glaziovianin A extended the time lag of tubulin polymerization without changing the net amount of polymerized tubulin in vitro and suppressed microtubule dynamics in cells. Furthermore, glaziovianin A inhibited the transport of endosomes containing EGF-stimulated EGFR and prolonged the EGFR activation. Consistent with the prolonged activation of EGFR, glaziovianin A enhanced the EGF-dependent apoptosis in A431 cells. These results strongly suggested that microtubule dynamics is important for endosome transport and maturation, and that glaziovianin A shows cytotoxicity by two pathways, the mitotic arrest and inadequate activation of receptor kinases via the inhibition of endosome maturation.