Cancer Immunology Immunotherapy,
Journal Year:
2024,
Volume and Issue:
73(3)
Published: Feb. 13, 2024
Abstract
T-cell
receptor
(TCR)
engineered
therapy
has
recently
emerged
as
a
promising
adoptive
immunotherapy
approach
for
tumor
treatment,
yet
hindered
by
immune
evasion
resulting
in
poor
therapeutic
efficacy.
The
introduction
of
ferroptosis-targeted
inducers
offers
potential
solution,
they
empower
T
cells
to
induce
ferroptosis
and
exert
influence
over
the
microenvironment.
Atovaquone
(ATO)
stands
prospective
pharmaceutical
candidate
with
target
ferroptosis,
effectively
provoking
an
excessive
generation
accumulation
reactive
oxygen
species
(ROS).
In
this
study,
we
evaluated
effectiveness
combination
comprising
ATO
TCR-T
against
hepatocellular
carcinoma
(HCC),
both
vitro
vivo.
results
lactate
dehydrogenase
cytokine
assays
demonstrated
that
enhanced
cytotoxicity
mediated
AFP-specific
promoted
release
IFN-
γ
vitro.
Additionally,
established
HCC
xenograft
mouse
model,
combined
low-dose
exhibited
heightened
efficacy
suppressing
growth,
no
apparent
adverse
effects,
comparable
achieved
through
monotherapy.
RNA-seq
data
unveiled
significant
activation
ferroptosis-related
pathway
group
comparison
group.
Mechanistically,
synergy
between
augmented
cells,
while
concurrently
elevating
intracellular
mitochondrial
levels
ROS,
expanding
labile
iron
pool,
impairing
integrity
membrane
HepG2
cells.
This
multifaceted
interaction
culminated
potentiation
within
tumor,
primarily
induced
excess
ROS.
summary,
co-administration
vulnerability
ferroptosis.
susceptibility
led
inhibition
growth
stimulation
anti-tumor
response.
These
findings
suggest
repurposing
atovaquone
cell
holds
enhance
treatment
outcomes
HCC.
Frontiers in Cell and Developmental Biology,
Journal Year:
2023,
Volume and Issue:
11
Published: Aug. 1, 2023
Reactive
oxygen
species
(ROS)
play
a
crucial
part
in
the
process
of
cell
death,
including
apoptosis,
autophagy,
and
ferroptosis.
ROS
involves
oxidation
lipids
generate
4-hydroxynonenal
other
compounds
associated
with
it.
Ferroptosis
may
be
facilitated
by
lipid
peroxidation
phospholipid
bilayers.
In
order
to
offer
novel
ideas
directions
for
investigation
disorders
connected
these
processes,
we
evaluate
function
which
ultimately
leads
ferroptosis
as
well
proposed
crosstalk
mechanisms
between
types
programmed
death.
Scientific Reports,
Journal Year:
2023,
Volume and Issue:
13(1)
Published: Sept. 19, 2023
Oxidative
stress
has
been
shown
to
induce
cell
death
in
a
wide
range
of
human
diseases
including
cardiac
ischemia/reperfusion
injury,
drug
induced
cardiotoxicity,
and
heart
failure.
However,
the
mechanism
by
oxidative
remains
incompletely
understood.
Here
we
provide
new
evidence
that
primarily
induces
ferroptosis,
but
not
apoptosis,
necroptosis,
or
mitochondria-mediated
necrosis,
cardiomyocytes.
Intriguingly,
organic
oxidants
such
as
tert-butyl
hydroperoxide
(tBHP)
cumene
(CHP),
hydrogen
peroxide
(H2O2),
promoted
glutathione
depletion
peroxidase
4
(GPX4)
degradation
cardiomyocytes,
leading
increased
lipid
peroxidation.
Moreover,
elevated
is
also
linked
labile
iron
overload
through
downregulation
transcription
suppressor
BTB
CNC
homology
1
(Bach1),
upregulation
heme
oxygenase
(HO-1)
expression,
enhanced
release
via
degradation.
Strikingly,
HO-1
translocation
mitochondria,
mitochondrial
reactive
oxygen
species
(ROS)
accumulation.
Targeted
inhibition
ROS
accumulation,
overexpressing
ferritin
(FTMT)
catalase
(mCAT),
respectively,
markedly
inhibited
stress-induced
ferroptosis.
The
levels
peroxides
were
cardiomyocytes
subjected
simulated
ischemia
reperfusion
(sI/R)
chemotherapeutic
agent
doxorubicin
(DOX).
Overexpressing
FTMT
mCAT
effectively
prevented
cardiomyocyte
sI/R
DOX.
Taken
together,
H2O2
triggers
ferroptotic
GPX4
Bach1/HO-1
dependent
mechanisms.
Our
results
reveal
key
well
potential
molecular
target
for
ferroptosis
Immunity,
Journal Year:
2024,
Volume and Issue:
57(5), P. 941 - 956
Published: May 1, 2024
Ferroptosis
is
a
type
of
regulated
cell
death
that
drives
the
pathophysiology
many
diseases.
Oxidative
stress
detectable
in
types
death,
but
only
ferroptosis
involves
lipid
peroxidation
and
iron
dependency.
originates
propagates
from
several
organelles,
including
mitochondria,
endoplasmic
reticulum,
Golgi,
lysosomes.
Recent
data
have
revealed
immune
cells
can
both
induce
undergo
ferroptosis.
A
mechanistic
understanding
how
regulates
immunity
critical
to
controls
responses
this
dysregulated
disease.
Translationally,
more
work
needed
produce
ferroptosis-modulating
immunotherapeutics.
This
review
focuses
on
role
immune-related
diseases,
infection,
autoimmune
cancer.
We
discuss
immunity,
regulation
contributes
disease
pathogenesis,
targeting
may
lead
novel
therapies.
Cells,
Journal Year:
2023,
Volume and Issue:
12(4), P. 611 - 611
Published: Feb. 13, 2023
Ferroptosis
induced
by
erastin
(an
inhibitor
of
cystine
transport)
and
butionine
sulfoximine
glutathione
biosynthesis)
was
prevented
the
mitochondria-targeted
antioxidants
SkQ1
MitoTEMPO.
These
effects
correlate
with
prevention
mitochondrial
lipid
peroxidation,
which
precedes
cell
death.
Methylene
blue,
a
redox
agent
that
inhibits
production
reactive
oxygen
species
(ROS)
in
complex
I
electron
transport
chain,
also
ferroptosis
peroxidation.
Activation
ROS
rotenone
presence
ferrous
iron
stimulates
peroxidation
isolated
mitochondria,
while
produced
III
are
ineffective.
methylene
blue
inhibit
We
suggest
formed
promote
ferroptosis.
Cancers,
Journal Year:
2024,
Volume and Issue:
16(3), P. 512 - 512
Published: Jan. 24, 2024
Iron
(Fe)
and
copper
(Cu),
essential
transition
metals,
play
pivotal
roles
in
various
cellular
processes
critical
to
cancer
biology,
including
cell
proliferation,
mitochondrial
respiration,
distant
metastases,
oxidative
stress.
The
emergence
of
ferroptosis
cuproptosis
as
distinct
forms
non-apoptotic
death
has
heightened
their
significance,
particularly
connection
with
these
metal
ions.
While
initially
studied
separately,
recent
evidence
underscores
the
interdependence
cuproptosis.
Studies
reveal
a
link
between
accumulation
induction.
This
interconnected
relationship
presents
promising
strategy,
especially
for
addressing
refractory
cancers
marked
by
drug
tolerance.
Harnessing
toxicity
iron
clinical
settings
becomes
crucial.
Simultaneous
targeting
cuproptosis,
exemplified
combination
sorafenib
elesclomol-Cu,
represents
an
intriguing
approach.
Strategies
mitochondria
further
enhance
precision
approaches,
providing
hope
improving
treatment
outcomes
drug-resistant
cancers.
Moreover,
chelators
copper-lowering
agents
established
therapeutic
modalities
exhibits
synergy
that
holds
promise
augmentation
anti-tumor
efficacy
malignancies.
review
elaborates
on
complex
interplay
underlying
mechanisms,
explores
potential
druggable
targets
both
research
settings.
Redox Biology,
Journal Year:
2024,
Volume and Issue:
71, P. 103087 - 103087
Published: Feb. 13, 2024
Ferroptosis,
an
iron-dependent
lipid
peroxidation-induced
form
of
regulated
cell
death,
shows
great
promise
as
a
cancer
therapy
strategy.
Despite
the
critical
role
mitochondria
in
ferroptosis
regulation,
underlying
mechanisms
remain
elusive.
This
study
reveals
that
mitochondrial
protein
METTL17
governs
function
colorectal
(CRC)
cells
through
epigenetic
modulation.
Bioinformatic
analysis
establishes
expression
positively
correlates
with
resistance
and
is
up-regulated
CRC.
Depletion
sensitizes
CRC
to
ferroptosis,
impairs
proliferation,
migration,
invasion,
xenograft
tumor
growth,
AOM/DSS-induced
tumorigenesis.
Furthermore,
suppression
disrupts
function,
energy
metabolism,
enhances
intracellular
peroxidation
ROS
levels
during
ferroptotic
stress.
Mechanistically,
inhibition
significantly
reduces
RNA
methylation,
including
m4C,
m5C,
m3C,
m7G,
m6A,
leading
impaired
translation
protein-coding
genes.
Additionally,
interacting
proteins
associated
are
essential
for
gene
expression,
their
knockdown
inhibits
proliferation.
Notably,
combined
targeting
therapeutic
approach
effectively
suppresses
growth
vivo.
uncovers
METTL17-mediated
defense
mechanism
survival
mitochondria,
highlighting
potential
target
