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HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D release and immunogenic cell death in primary effusion lymphoma.
[primary effusion lymphoma]
Heat-shock
protein
(
HSP
)
70
is
aberrantly
expressed
in
different
malignancies
and
has
a
cancer
-
specific
cell-protective
effect
.
As
such
,
it
has
emerged
as
a
promising
target
for
anticancer
therapy
.
In
this
study
,
the
effect
of
the
HSP
70
-
specific
inhibitor
(
PES
)
,
also
Pifitrin-μ
,
on
primary
effusion
lymphoma
(
PEL
)
cell
viability
was
analyzed
.
PES
treatment
induced
a
dose-
and
time-dependent
cytotoxic
effect
in
BC
3
and
BCBL
1
PEL
cells
by
inducing
lysosome
membrane
permeabilization
,
relocation
of
cathepsin
D
in
the
cytosol
,
Bid
cleavage
,
mitochondrial
depolarization
with
release
and
nuclear
translocation
of
apoptosis-activating
factor
.
The
PES-induced
cell
death
in
PEL
cells
was
characterized
by
the
appearance
of
Annexin-
V
/
propidium
iodide
double
-
positive
cells
from
the
early
times
of
treatment
,
indicating
the
occurrence
of
an
additional
type
of
cell
death
other
than
apoptosis
,
which
,
accordingly
,
was
not
efficiently
prevented
by
the
pan-caspase
inhibitor
Z-VAD-fmk
.
Conversely
,
PES-induced
cell
death
was
robustly
reduced
by
pepstatin
A
,
which
inhibits
Bid
and
caspase
8
processing
.
In
addition
,
PES
was
responsible
for
a
block
of
the
autophagic
process
in
PEL
cells
.
Finally
,
we
found
that
PES-induced
cell
death
has
immunogenic
potential
being
able
to
induce
dendritic
cell
activation
.
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