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Luteolin, ellagic acid and punicic acid are natural products that inhibit prostate cancer metastasis.
[severe combined immunodeficiency]
Prostate
cancer
(
PCa
)
is
the
second
cause
of
cancer
deaths
in
men
in
the
USA
.
When
the
cancer
recurs
,
early
stages
can
be
controlled
with
hormone
ablation
therapy
to
delay
the
rate
of
cancer
progression
but
,
over
time
,
the
cancer
overcomes
its
hormone
dependence
,
becomes
highly
aggressive
and
metastasizes
.
Clinical
trials
have
shown
that
pomegranate
juice
(
PJ
)
inhibits
PCa
progression
.
We
have
previously
shown
that
the
PJ
components
luteolin
(
L
)
,
ellagic
acid
(
E
)
and
punicic
acid
(
P
)
together
inhibit
growth
of
hormone-dependent
and
-
independent
PCa
cells
and
inhibit
their
migration
and
chemotaxis
towards
CXCL
12
,
a
chemokine
that
is
important
in
PCa
metastasis
.
On
the
basis
of
these
findings
,
we
hypothesized
that
L
+
E
+
P
inhibit
PCa
metastasis
in
vivo
.
To
test
this
possibility
,
we
used
a
severe
combined
immunodeficiency
mouse
model
in
which
luciferase-expressing
human
PCa
cells
were
injected
subcutaneously
near
the
prostate
.
Tumor
progression
was
monitored
with
bioluminescence
imaging
weekly
.
We
found
that
L
+
E
+
P
inhibits
PC
-
3
M
-
luc
primary
tumor
growth
,
inhibits
the
CXCL
12
/
CXCR
4
axis
for
metastasis
and
none
of
the
tumors
metastasized
.
In
addition
,
L
+
E
+
P
significantly
inhibits
growth
and
metastasis
of
highly
invasive
Pten
(
-
/
-
)
;
K-
ras
(
G
12
D
)
prostate
tumors
.
Furthermore
,
L
+
E
+
P
inhibits
angiogenesis
in
vivo
,
prevents
human
endothelial
cell
(
EC
)
tube
formation
in
culture
and
disrupts
preformed
EC
tubes
,
indicating
inhibition
of
EC
adhesion
to
each
other
.
L
+
E
+
P
also
inhibits
the
angiogenic
factors
interleukin-
8
and
vascular
endothelial
growth
factor
as
well
as
their
induced
signaling
pathways
in
ECs
.
In
conclusion
,
these
results
show
that
L
+
E
+
P
inhibits
PCa
progression
and
metastasis
.
Diseases
Validation
Diseases presenting
"significantly inhibits growth"
symptom
severe combined immunodeficiency
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