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Urokinase-type plasminogen activator expression and Rac1/WAVE-2/Arp2/3 pathway are blocked by pterostilbene to suppress cell migration and invasion in MDA-MB-231 cells.
[wiskott-aldrich syndrome]
Breast
cancer
is
the
most
common
malignancy
among
females
,
and
cancer
invasion
and
metastasis
are
the
leading
causes
of
cancer
death
in
breast
cancer
patients
.
Pterostilbene
,
a
naturally
occurring
dimethylether
analogue
of
resveratrol
,
has
been
demonstrated
to
possess
anti-
cancer
effects
.
However
,
inhibitory
effects
of
pterostilbene
on
cell
migration
and
invasion
and
its
underlying
mechanisms
are
not
fully
understood
.
In
this
study
,
we
investigated
the
anti-invasive
mechanisms
of
pterostilbene
in
human
breast
cancer
cell
line
MDA-
MB
-
231
cells
.
Pterostilbene
effectively
inhibited
serum-induced
migration
and
invasion
without
affecting
the
viability
of
breast
cancer
cells
.
The
mRNA
expression
and
activity
of
urokinase-
type
plasminogen
activator
(
uPA
)
were
markedly
reduced
by
pterostilbene
treatment
.
Moreover
,
pterostilbene
attenuated
nuclear
factor
κB
(
NF-κB
)
transcriptional
activity
and
DNA
binding
of
NF-κB
on
uPA
promoter
.
In
addition
,
pterostilbene
significantly
impaired
the
activity
of
Rac
1
and
the
expression
of
WASP-family
verprolin-homologous
protein-
2
(
WAVE-
2
)
and
actin-related
protein
2
/
3
(
Arp
2
/
3
)
.
Overall
,
these
results
suggest
that
pterostilbene
caused
considerable
suppression
of
cell
migration
and
invasion
through
blocking
NF-κB-mediated
uPA
expression
and
Rac
1
/
WAVE
/
Arp
2
/
3
pathway
.
