Hepatocellular
carcinoma
(HCC)
is
the
most
common
lethal
form
of
liver
cancer.
Apart
from
surgical
removal
and
transplantation,
other
treatments
have
not
yet
been
well
established
for
patients
with
HCC.
In
this
study,
we
found
that
carboxylesterase
1
(CES1)
expressed
at
various
levels
in
We
further
revealed
blockage
CES1
by
pharmacological
genetical
approaches
leads
to
altered
lipid
profiles
are
directly
linked
impaired
mitochondrial
function.
Mechanistically,
lipidomic
analyses
indicated
signaling
molecules,
including
polyunsaturated
fatty
acids
(PUFAs),
which
activate
PPARα/γ,
were
dramatically
reduced
upon
inhibition.
As
a
result,
expression
SCD,
PPARα/γ
target
gene
involved
tumor
progression
chemoresistance,
was
significantly
downregulated.
Clinical
analysis
demonstrated
strong
correlation
between
protein
SCD
Interference
targeting
CES1-PPARα/γ-SCD
axis
sensitized
HCC
cells
cisplatin
treatment.
growth
xenograft
tumors
NU/J
mice
potently
slowed
coadministration
Our
results,
thus,
suggest
promising
therapeutic
Journal of Hematology & Oncology,
Год журнала:
2023,
Номер
16(1)
Опубликована: Сен. 12, 2023
Abstract
Lipid
metabolic
reprogramming
is
an
emerging
hallmark
of
cancer.
In
order
to
sustain
uncontrolled
proliferation
and
survive
in
unfavorable
environments
that
lack
oxygen
nutrients,
tumor
cells
undergo
transformations
exploit
various
ways
acquiring
lipid
increasing
oxidation.
addition,
stromal
immune
the
microenvironment
also
reprogramming,
which
further
affects
functional
phenotypes
responses.
Given
metabolism
plays
a
critical
role
supporting
cancer
progression
remodeling
microenvironment,
targeting
pathway
could
provide
novel
approach
treatment.
This
review
seeks
to:
(1)
clarify
overall
landscape
mechanisms
cancer,
(2)
summarize
landscapes
within
their
roles
progression,
(3)
potential
therapeutic
targets
for
metabolism,
highlight
combining
such
approaches
with
other
anti-tumor
therapies
new
opportunities
patients.
Cell Proliferation,
Год журнала:
2021,
Номер
54(11)
Опубликована: Сен. 25, 2021
Abstract
Objectives
Chondrocyte
ferroptosis
contributes
to
osteoarthritis
(OA)
progression,
and
D‐mannose
shows
therapeutic
value
in
many
inflammatory
conditions.
Here,
we
investigated
whether
interferes
chondrocyte
ferroptotic
cell
death
during
osteoarthritic
cartilage
degeneration.
Materials
methods
In
vivo
anterior
cruciate
ligament
transection
(ACLT)‐induced
OA
mouse
model
an
vitro
study
of
chondrocytes
microenvironment
induced
by
interleukin‐1β
(IL‐1β)
exposure
were
employed.
Combined
with
Epas1
gene
gain‐
loss‐of‐function,
histology,
immunofluorescence,
quantitative
RT‐PCR,
Western
blot,
viability
flow
cytometry
experiments
performed
evaluate
the
chondroprotective
effects
progression
role
hypoxia‐inducible
factor
2
alpha
(HIF‐2
α)
D‐mannose‐induced
resistance
chondrocytes.
Results
exerted
a
effect
attenuating
sensitivity
alleviated
progression.
HIF‐2α
was
identified
as
central
mediator
Furthermore,
overexpression
Ad‐
intra‐articular
injection
abolished
eliminated
suppressor.
Conclusions
alleviates
suppressing
HIF‐2α‐mediated
ferroptosis,
indicating
be
potential
strategy
for
ferroptosis‐related
diseases.
Cell Death and Disease,
Год журнала:
2023,
Номер
14(7)
Опубликована: Июль 25, 2023
Ferroptosis,
a
programmed
cell
death,
has
been
identified
and
associated
with
cancer
various
other
diseases.
Ferroptosis
is
defined
as
reactive
oxygen
species
(ROS)-dependent
death
related
to
iron
accumulation
lipid
peroxidation,
which
different
from
apoptosis,
necrosis,
autophagy,
forms
of
death.
However,
accumulating
evidence
revealed
link
between
autophagy
ferroptosis
at
the
molecular
level
suggested
that
involved
in
regulating
iron-dependent
peroxidation
ROS
during
ferroptosis.
Understanding
roles
pathophysiological
processes
may
provide
effective
strategies
for
treatment
ferroptosis-related
In
this
review,
we
summarize
current
knowledge
regarding
regulatory
mechanisms
underlying
ferroptosis,
including
metabolism,
its
association
pathway.
addition,
discuss
contribution
elucidate
role
enhancer
ROS-dependent
Abstract
Lipid
metabolism
is
a
complex
biochemical
process
that
participates
in
the
regulation
of
cell
survival
and
death.
Ferroptosis
form
iron‐dependent
regulated
death
driven
by
abnormal
lipid
metabolism,
leading
to
peroxidation
subsequent
plasma
membrane
rupture.
A
variety
antioxidant
systems
repair
pathways
can
diminish
oxidative
damage,
enabling
growth
response
ferroptotic
signals.
Such
impairment
ferroptosis
machinery
implicated
various
pathological
conditions
diseases,
especially
cancer
tissue
damage.
It
discussed
here
how
pathways,
including
synthesis,
degradation,
storage,
transformation,
utilization,
modulate
sensitivity
or
tolerance
different
models,
cancer.
Frontiers in Cell and Developmental Biology,
Год журнала:
2023,
Номер
11
Опубликована: Янв. 27, 2023
Lipid
droplets
are
fat
storage
organelles
ubiquitously
distributed
across
the
eukaryotic
kingdom.
They
have
a
central
role
in
regulating
lipid
metabolism
and
undergo
dynamic
turnover
of
biogenesis
breakdown
to
meet
cellular
requirements
for
fatty
acids,
including
polyunsaturated
acids.
Polyunsaturated
acids
esterified
membrane
phospholipids
define
fluidity
can
be
released
by
activity
phospholipases
A
Cancer Communications,
Год журнала:
2024,
Номер
44(2), С. 185 - 204
Опубликована: Янв. 13, 2024
Abstract
Cellular
metabolism
is
the
fundamental
process
by
which
cells
maintain
growth
and
self‐renewal.
It
produces
energy,
furnishes
raw
materials,
intermediates
for
biomolecule
synthesis,
modulates
enzyme
activity
to
sustain
normal
cellular
functions.
foundation
of
life
processes
plays
a
regulatory
role
in
various
biological
functions,
including
programmed
cell
death.
Ferroptosis
recently
discovered
form
iron‐dependent
The
inhibition
ferroptosis
crucial
tumorigenesis
tumor
progression.
However,
metabolism,
particularly
glucose
amino
acid
cancer
not
well
understood.
Here,
we
reviewed
glucose,
lipid,
acid,
iron
selenium
involvement
elucidate
impact
different
metabolic
pathways
on
this
process.
Additionally,
provided
detailed
overview
agents
used
induce
ferroptosis.
We
explained
that
maintaining
intracellular
redox
homeostasis
disrupting
these
renders
them
more
susceptible
iron‐induced
death,
resulting
enhanced
killing.
combination
inducers
inhibitors
may
be
novel
approach
future
therapy
an
important
strategy
advance
development
treatments.
Journal of Translational Medicine,
Год журнала:
2024,
Номер
22(1)
Опубликована: Март 18, 2024
Abstract
Lipid
metabolism
is
widely
reprogrammed
in
tumor
cells.
droplet
a
common
organelle
existing
most
mammal
cells,
and
its
complex
dynamic
functions
maintaining
redox
metabolic
balance,
regulating
endoplasmic
reticulum
stress,
modulating
chemoresistance,
providing
essential
biomolecules
ATP
have
been
well
established
The
balance
between
lipid
formation
catabolism
critical
to
energy
while
the
process
of
affects
various
for
growth.
imbalance
synthesis
fatty
acids
cells
leads
alteration
content
Diacylglycerol
acyltransferase
1
diacylglycerol
2,
enzymes
that
catalyze
final
step
triglyceride
synthesis,
participate
droplets
regulation
cell
proliferation,
migration
invasion,
prognosis
tumor.
Several
2
inhibitors
developed
over
past
decade
shown
anti-tumor
effects
preclinical
models
improvement
clinical
trials.
In
this
review,
we
highlight
key
features
acid
different
paradigms
activities
on
migration,
tumor,
with
hope
these
scientific
findings
will
potential
implications.
