Glaziovianin A Prevents Endosome Maturation <i>via</i> Inhibiting Microtubule Dynamics
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Abstract
Glaziovianin A, an isoflavone isolated
from the leaves of <i>Ateleia glazioviana</i>, 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 <i>in vitro</i> 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 <i>via</i> the inhibition
of endosome maturation