Glaziovianin a prevents endosome maturation via inhibiting microtubule dynamics

Takumi Chinen, Sayaka Kazami, Yoko Nagumo, Ichiro Hayakawa, Akiyuki Ikedo, Masatoshi Takagi, Akihito Yokosuka, Naoko Imamoto, Yoshihiro Mimaki, Hideo Kigoshi, Hiroyuki Osada, Takeo Usui

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)884-889
Number of pages6
JournalACS Chemical Biology
Volume8
Issue number5
DOIs
Publication statusPublished - May 17 2013
Externally publishedYes

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Endosomes
Microtubules
Chemical activation
Tubulin
Epidermal Growth Factor
Isoflavones
Cytotoxicity
Polymerization
Cell Division
glaziovianin A
Cell Cycle
Phosphotransferases
Cells
Apoptosis
Derivatives

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Medicine(all)

Cite this

Chinen, T., Kazami, S., Nagumo, Y., Hayakawa, I., Ikedo, A., Takagi, M., ... Usui, T. (2013). Glaziovianin a prevents endosome maturation via inhibiting microtubule dynamics. ACS Chemical Biology, 8(5), 884-889. https://doi.org/10.1021/cb300641h

Glaziovianin a prevents endosome maturation via inhibiting microtubule dynamics. / Chinen, Takumi; Kazami, Sayaka; Nagumo, Yoko; Hayakawa, Ichiro; Ikedo, Akiyuki; Takagi, Masatoshi; Yokosuka, Akihito; Imamoto, Naoko; Mimaki, Yoshihiro; Kigoshi, Hideo; Osada, Hiroyuki; Usui, Takeo.

In: ACS Chemical Biology, Vol. 8, No. 5, 17.05.2013, p. 884-889.

Research output: Contribution to journalArticle

Chinen, T, Kazami, S, Nagumo, Y, Hayakawa, I, Ikedo, A, Takagi, M, Yokosuka, A, Imamoto, N, Mimaki, Y, Kigoshi, H, Osada, H & Usui, T 2013, 'Glaziovianin a prevents endosome maturation via inhibiting microtubule dynamics', ACS Chemical Biology, vol. 8, no. 5, pp. 884-889. https://doi.org/10.1021/cb300641h
Chinen, Takumi ; Kazami, Sayaka ; Nagumo, Yoko ; Hayakawa, Ichiro ; Ikedo, Akiyuki ; Takagi, Masatoshi ; Yokosuka, Akihito ; Imamoto, Naoko ; Mimaki, Yoshihiro ; Kigoshi, Hideo ; Osada, Hiroyuki ; Usui, Takeo. / Glaziovianin a prevents endosome maturation via inhibiting microtubule dynamics. In: ACS Chemical Biology. 2013 ; Vol. 8, No. 5. pp. 884-889.
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