title: Glaziovianin A prevents endosome maturation via inhibiting microtubule dynamics.
abstract: 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.
authors: Takumi
authors: T
authors: Chinen
authors: Sayaka
authors: S
authors: Kazami
authors: Yoko
authors: Y
authors: Nagumo
authors: Ichiro
authors: I
authors: Hayakawa
authors: Akiyuki
authors: A
authors: Ikedo
authors: Masatoshi
authors: M
authors: Takagi
authors: Akihito
authors: A
authors: Yokosuka
authors: Naoko
authors: N
authors: Imamoto
authors: Yoshihiro
authors: Y
authors: Mimaki
authors: Hideo
authors: H
authors: Kigoshi
authors: Hiroyuki
authors: H
authors: Osada
authors: Takeo
authors: T
authors: Usui
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; D014404:Tubulin; D050257:Tubulin Modulators; C521560:glaziovianin A; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors