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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
"tumor progression"
symptom
carcinoma of the gallbladder
cholangiocarcinoma
dedifferentiated liposarcoma
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
liposarcoma
pleomorphic liposarcoma
severe combined immunodeficiency
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
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