6 research outputs found
Glaziovianin A Prevents Endosome Maturation <i>via</i> Inhibiting Microtubule Dynamics
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
Glaziovianin A Prevents Endosome Maturation <i>via</i> Inhibiting Microtubule Dynamics
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
Glaziovianin A Prevents Endosome Maturation <i>via</i> Inhibiting Microtubule Dynamics
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
Glaziovianin A Prevents Endosome Maturation <i>via</i> Inhibiting Microtubule Dynamics
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
Glaziovianin A Prevents Endosome Maturation <i>via</i> Inhibiting Microtubule Dynamics
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
Vicenistatin induces early endosome-derived vacuole formation in mammalian cells
<p>Homotypic fusion of early endosomes is important for efficient protein trafficking and sorting. The key controller of this process is Rab5 which regulates several effectors and PtdInsPs levels, but whose mechanisms are largely unknown. Here, we report that vicenistatin, a natural product, enhanced homotypic fusion of early endosomes and induced the formation of large vacuole-like structures in mammalian cells. Unlike YM201636, another early endosome vacuolating compound, vicenistatin did not inhibit PIKfyve activity <i>in vitro</i> but activated Rab5-PAS pathway in cells. Furthermore, vicenistatin increased the membrane surface fluidity of cholesterol-containing liposomes <i>in vitro</i>, and cholesterol deprivation from the plasma membrane stimulated vicenistatin-induced vacuolation in cells. These results suggest that vicenistatin is a novel compound that induces the formation of vacuole-like structures by activating Rab5-PAS pathway and increasing membrane fluidity.</p> <p>Vicenistatin is a novel compound that induces the formation of vacuole-like structures by activating Rab5-PAS pathway and increasing membrane fluidity.</p