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JNK and macroautophagy activation by bortezomib has a pro-survival effect in primary effusion lymphoma cells.
[primary effusion lymphoma]
Understanding
the
mechanisms
of
autophagy
induction
and
its
role
during
chemotherapeutic
treatments
is
of
fundamental
importance
in
order
to
manipulate
it
to
improve
the
outcome
of
chemotherapy
.
In
particular
whether
the
bortezomib-induced
autophagy
plays
a
pro-survival
or
pro-death
role
is
still
controversial
.
In
this
study
we
investigated
if
bortezomib
induced
endoplasmic
reticulum
(
ER
)
stress
and
activated
autophagy
in
Primary
Effusion
Lymphoma
(
PEL
)
cells
and
how
they
influenced
cell
survival
.
We
found
that
bortezomib
induced
up-regulation
of
the
pro-survival
and
pro-death
ER
stress
molecules
BIP
and
CHOP
and
activated
c-
Jun
NH
2
-
terminal
kinase
(
JNK
)
,
resulting
in
Bcl-
2
phosphorylation
and
induction
of
autophagy
.
JNK
and
autophagy
activation
played
a
pro-survival
role
in
this
setting
,
thus
their
inhibition
increased
the
bortezomib
cytotoxic
effect
and
PARP
cleavage
in
PEL
cells
.
Based
on
our
results
we
suggest
that
the
combination
of
bortezomib
with
JNK
or
autophagy
inhibitors
could
be
exploited
to
improve
the
outcome
of
therapy
of
this
aggressive
B
cell
lymphoma
.
Diseases
Validation
Diseases presenting
"b cell lymphoma"
symptom
hodgkin lymphoma, classical
primary effusion lymphoma
This symptom has already been validated
