Abstract
High
cobalt
(Co)
levels
in
tumors
are
associated
with
good
clinical
prognosis.
An
anticancer
regimen
that
increases
intratumoral
Co
through
targeted
nanomaterial
delivery
is
proposed
this
study.
Bovine
serum
albumin
and
dichloride
applied
to
prepare
cobaltous
oxide
nanodots
using
a
facile
biomineralization
strategy.
After
iRGD
peptide
conjugation,
the
loaded
into
dendritic
mesoporous
silica
nanoparticles,
generating
biocompatible
product
iCoDMSN.
This
nanocomposite
accumulates
after
intravenous
injection
by
deep
tissue
penetration
can
be
used
for
photoacoustic
imaging.
Proteomics
research
molecular
biology
experiments
reveal
iCoDMSN
potent
ferroptosis
inducer
cancer
cells.
Mechanistically,
iCoDMSNs
upregulate
heme
oxygenase
1
(HMOX1),
which
transferrin
receptors
reduces
solute
carrier
family
40
member
(SLC40A1),
resulting
Fe
2+
accumulation
initiation.
Furthermore,
upregulated
nuclear
factor
erythroid
2‐related
2
(NRF2),
arising
from
reduction
Kelch‐like
ECH‐associated
protein
(KEAP1)
expression,
responsible
HMOX1
enhancement
treatment.
Owing
intensified
ferroptosis,
acts
as
an
efficient
radiotherapy
enhancer
eliminate
cells
vitro
vivo.
study
demonstrates
versatile
Co‐based
primes
expanding
labile
iron
pool
cells,
providing
promising
tumor
sensitizer.
The Journal of Cell Biology,
Год журнала:
2021,
Номер
220(9)
Опубликована: Июль 30, 2021
Ferroptosis
is
a
form
of
iron-dependent
regulated
cell
death
driven
by
uncontrolled
lipid
peroxidation.
Mitochondria
are
double-membrane
organelles
that
have
essential
roles
in
energy
production,
cellular
metabolism,
and
regulation.
However,
their
role
ferroptosis
has
been
unclear
somewhat
controversial.
In
this
Perspective,
I
summarize
the
diverse
metabolic
processes
mitochondria
actively
drive
ferroptosis,
discuss
recently
discovered
mitochondria-localized
defense
systems
detoxify
mitochondrial
peroxides
protect
against
present
new
evidence
for
regulating
outline
outstanding
questions
on
fascinating
topic
future
investigations.
An
in-depth
understanding
functions
will
important
implications
both
fundamental
biology
disease
treatment.
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Апрель 22, 2022
Targeting
ferroptosis,
a
unique
cell
death
modality
triggered
by
unrestricted
lipid
peroxidation,
in
cancer
therapy
is
hindered
our
incomplete
understanding
of
ferroptosis
mechanisms
under
specific
genetic
contexts.
KEAP1
(kelch-like
ECH
associated
protein
1)
frequently
mutated
or
inactivated
lung
cancers,
and
mutant
cancers
are
refractory
to
most
therapies,
including
radiotherapy.
In
this
study,
we
identify
suppressor
1
(FSP1,
also
known
as
AIFM2)
transcriptional
target
nuclear
factor
erythroid
2-related
2
(NRF2)
reveal
that
the
ubiquinone
(CoQ)-FSP1
axis
mediates
ferroptosis-
radiation-
resistance
deficient
cells.
We
further
show
pharmacological
inhibition
CoQ-FSP1
sensitizes
cells
patient-derived
xenograft
tumors
radiation
through
inducing
ferroptosis.
Together,
study
identifies
key
downstream
effector
KEAP1-NRF2
pathway
potential
therapeutic
for
treating
cancers.
Journal of Translational Medicine,
Год журнала:
2021,
Номер
19(1)
Опубликована: Авг. 26, 2021
Abstract
Background
Solute
carrier
family
7
member
11(SLC7A11)
is
a
component
of
cysteine/glutamate
transporter,
which
plays
key
role
in
tumor
growth;
however,
its
underlying
effect
on
radiosensitivity
esophageal
squamous
cell
carcinoma
(ESCC)
remains
unclear.
This
study
aimed
to
clarify
SLC7A11’s
expression
and
correlation
with
nuclear
factor
erythroid-2
(
NRF2)-associated
radioresistance
ESCC.
Methods
We
included
127
ESCC
patients
who
received
radical
chemoradiotherapy.
Immunohistochemical
staining
was
used
detect
SLC7A11
NRF2
expression,
the
relationship
between
clinicopathological
characteristics
survival
rates
or
therapy
response
were
evaluated.
Western
blot,
dual-reporter
assays
Chromatin
immunoprecipitation
(ChIP)-sequencing
analyze
their
vitro.
Their
roles
then
investigated
through
multiple
validation
steps.
Results
overexpressed
tissues
positively
correlated
one
another.
significantly
associated
length,
lymph
node
metastasis,
TNM
stage,
while
metastasis.
Patients
high
had
shorter
overall
progression-free
survival,
poor
treatment
response.
The
multivariate
model
showed
that
sex
location
are
independent
prognostic
factors.
In
vitro
analysis
confirmed
hyperactivation
induced
by
directly
binding
promoter
region,
promoting
radioresistance,
reducing
radiotherapy-induced
lipid
peroxidation
levels,
PTGS2
radiotherapy-related
ferroptosis
morphologic
features.
Conclusion
Our
reveals
connection
related
worse
poorer
outcomes.
SLC7A11-mediated
inhibition
NRF2-associated
highlighting
potential
NRF2/SLC7A11/ferroptosis
axis
as
future
therapeutic
targets
against
resistance
biomarker.
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Март 8, 2024
Ferroptosis
is
a
non-apoptotic
form
of
regulated
cell
death
characterized
by
the
lethal
accumulation
iron-dependent
membrane-localized
lipid
peroxides.
It
acts
as
an
innate
tumor
suppressor
mechanism
and
participates
in
biological
processes
tumors.
Intriguingly,
mesenchymal
dedifferentiated
cancer
cells,
which
are
usually
resistant
to
apoptosis
traditional
therapies,
exquisitely
vulnerable
ferroptosis,
further
underscoring
its
potential
treatment
approach
for
cancers,
especially
refractory
cancers.
However,
impact
ferroptosis
on
extends
beyond
direct
cytotoxic
effect
cells.
induction
not
only
inhibits
but
also
promotes
development
due
negative
anticancer
immunity.
Thus,
comprehensive
understanding
role
crucial
successful
translation
therapy
from
laboratory
clinical
applications.
In
this
review,
we
provide
overview
recent
advancements
cancer,
covering
molecular
mechanisms,
functions,
regulatory
pathways,
interactions
with
microenvironment.
We
summarize
applications
immunotherapy,
radiotherapy,
systemic
therapy,
well
inhibition
various
conditions.
finally
discuss
markers,
current
challenges
future
directions
cancer.
Journal of Advanced Research,
Год журнала:
2022,
Номер
41, С. 63 - 75
Опубликована: Янв. 11, 2022
Excessive
mechanical
stress
is
closely
associated
with
cell
death
in
various
conditions.
Exposure
of
chondrocytes
to
excessive
loading
leads
a
catabolic
response
as
well
exaggerated
death.
Ferroptosis
recently
identified
form
during
aging
and
degeneration.
However,
it's
potential
association
remains
be
illustrated.To
identify
whether
can
cause
ferroptosis.
To
explore
the
role
overloading
chondrocyte
ferroptosis.Chondrocytes
were
collected
from
unloading
zones
cartilage
patients
osteoarthritis
(OA),
ferroptosis
phenotype
was
analyzed
through
transmission
electron
microscope
microarray.
Moreover,
relationship
between
OA
by
GPX4-conditional
knockout
(Col2a1-CreERT:
GPX4flox/flox)
mice
model
cultured
high
strain
stress.
Furthermore,
Piezo1
ion
channel
development
explored
using
its
inhibitor
(GsMTx4)
agonist
(Yoda1).
Additionally,
calcium-free
medium
stress,
tested.Human
mouse
experiments
revealed
that
induce
GPX4-associated
Conditional
GPX4
aggravated
experimental
process,
while
additional
treatment
suppressor
protein
(FSP-1)
coenzyme
Q10
(CoQ10)
abated
GPX4-CKO
mice.
In
experiments,
inhibition
activity
increased
expression,
attenuated
reduced
severity
osteoarthritis.
induced
damage
largely
abolished
blocking
calcium
influx
medium.Our
findings
show
induces
activation
subsequent
chondrocytes,
which
might
provide
target
for
treatment.
