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Hippuristanol reduces the viability of primary effusion lymphoma cells both in vitro and in vivo.
[primary effusion lymphoma]
Primary
effusion
lymphoma
(
PEL
)
caused
by
Kaposi
's
sarcoma
-associated
herpesvirus
(
also
known
as
human
herpesvirus-
8
)
shows
serious
lymphomatous
effusion
in
body
cavities
.
PEL
is
difficult
to
treat
and
there
is
no
standard
treatment
strategy
.
Hippuristanol
is
extracted
from
Okinawan
coral
Isis
hippuris
,
and
inhibits
translational
initiation
by
blocking
eukaryotic
initiation
factor
4
A
,
an
ATP-dependent
RNA
helicase
,
binding
to
mRNA
.
Recently
,
there
has
been
much
interest
in
targeting
translation
initiation
as
an
anticancer
therapy
.
Here
,
we
show
that
treatment
of
PEL
cell
lines
with
hippuristanol
resulted
in
cell
cycle
arrest
at
G
1
phase
,
and
induced
caspases
activation
and
apoptosis
.
Hippuristanol
also
reduced
the
expression
of
cyclin
D
2
,
CDK
2
,
CDK
4
,
CDK
6
and
prosurvival
XIAP
and
Mcl-
1
proteins
.
Activation
of
activator
protein-
1
,
signal
transducers
and
activators
of
transcription
protein
3
and
Akt
pathways
plays
a
critical
role
in
the
survival
and
growth
of
PEL
cells
.
Hippuristanol
suppressed
the
activities
of
these
three
pathways
by
inhibiting
the
expression
of
JunB
,
JunD
,
c-
Fos
,
signal
transducers
and
activators
of
transcription
protein
3
and
Akt
proteins
.
In
a
xenograft
mouse
model
that
showed
ascites
and
diffused
organ
invasion
of
PEL
cells
,
treatment
with
hippuristanol
significantly
inhibited
the
growth
and
invasion
of
PEL
cells
compared
with
untreated
mice
.
The
results
of
the
in
vitro
and
in
vivo
experiments
underline
the
potential
usefulness
of
hippuristanol
in
the
treatment
of
PEL
.
Diseases
Validation
Diseases presenting
"lymphoma"
symptom
adrenal incidentaloma
alpha-thalassemia
carcinoma of the gallbladder
cushing syndrome
dedifferentiated liposarcoma
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
familial hypocalciuric hypercalcemia
focal myositis
hirschsprung disease
hodgkin lymphoma, classical
kabuki syndrome
liposarcoma
locked-in syndrome
monosomy 21
oculocutaneous albinism
primary effusion lymphoma
severe combined immunodeficiency
systemic capillary leak syndrome
waldenström macroglobulinemia
wiskott-aldrich syndrome
This symptom has already been validated