Aging,
Год журнала:
2023,
Номер
15(22), С. 12952 - 12965
Опубликована: Ноя. 16, 2023
Colorectal
cancer
is
one
of
the
most
common
malignant
tumors
in
digestive
system,
and
its
high
incidence
metastasis
rate
make
it
a
terrible
killer
that
threatens
human
health.
In-depth
exploration
targets
affecting
progression
colorectal
cells
development
specific
targeted
drugs
for
them
are
great
significance
prognosis
patients.
Erythropoietin-producing
hepatocellular
A2
(EphA2)
member
Eph
subfamily
with
tyrosine
kinase
activity,
plays
key
role
regulation
signaling
pathways
related
to
phenotype
various
tumor
cells,
but
regulatory
mechanism
needs
be
further
clarified.
Here,
we
found
EphA2
was
abnormally
highly
expressed
patients
expression
had
worse
prognosis.
We
also
can
form
liquid-liquid
phase
separation
condensates
on
cell
membrane,
which
disrupted
by
ALW-II-41-27,
an
inhibitor
EphA2.
In
addition,
positively
correlated
ferroptosis-related
genes
infiltration
multiple
immune
cells.
These
findings
suggest
novel
membrane
protein
ability
associated
ferroptosis
infiltration,
suggests
may
inhibited
suppressing
Molecular Cell,
Год журнала:
2024,
Номер
84(23), С. 4629 - 4644.e9
Опубликована: Ноя. 14, 2024
Selenium-dependent
glutathione
peroxidase
4
(GPX4)
is
the
guardian
of
ferroptosis,
preventing
unrestrained
(phospho)lipid
peroxidation
by
reducing
phospholipid
hydroperoxides
(PLOOH).
However,
contribution
other
peroxidases
in
ferroptosis
protection
remains
unclear.
We
show
that
cells
lacking
GPX4
still
exhibit
substantial
PLOOH-reducing
capacity,
suggesting
a
alternative
PLOOH
peroxidases.
By
scrutinizing
potential
candidates,
we
found
although
overexpression
peroxiredoxin
6
(PRDX6),
thiol-specific
antioxidant
enzyme
with
reported
activity,
failed
to
prevent
its
genetic
loss
sensitizes
cancer
ferroptosis.
Mechanistically,
uncover
PRDX6,
beyond
known
acts
as
selenium-acceptor
protein,
facilitating
intracellular
selenium
utilization
and
efficient
incorporation
into
selenoproteins,
including
GPX4.
Its
physiological
significance
was
demonstrated
reduced
expression
Prdx6-deficient
mouse
brains
increased
sensitivity
PRDX6-deficient
tumor
xenografts
mice.
Our
study
highlights
PRDX6
critical
player
directing
cellular
dictating
sensitivity.
Acta Pharmaceutica Sinica B,
Год журнала:
2024,
Номер
14(7), С. 2815 - 2853
Опубликована: Апрель 24, 2024
Regulated
cell
death
(RCD)
is
a
controlled
form
of
orchestrated
by
one
or
more
cascading
signaling
pathways,
making
it
amenable
to
pharmacological
intervention.
RCD
subroutines
can
be
categorized
as
apoptotic
non-apoptotic
and
play
essential
roles
in
maintaining
homeostasis,
facilitating
development,
modulating
immunity.
Accumulating
evidence
has
recently
revealed
that
evasion
frequently
the
primary
cause
tumor
survival.
Several
have
garnered
attention
promising
cancer
therapies
due
their
ability
induce
regression
prevent
relapse,
comparable
apoptosis.
Moreover,
they
offer
potential
solutions
for
overcoming
acquired
resistance
tumors
toward
drugs.
With
an
increasing
understanding
underlying
mechanisms
governing
these
subroutines,
growing
number
small-molecule
compounds
targeting
single
multiple
pathways
been
discovered,
providing
novel
strategies
current
therapy.
In
this
review,
we
comprehensively
summarized
regulatory
emerging
mainly
including
autophagy-dependent
death,
ferroptosis,
cuproptosis,
disulfidptosis,
necroptosis,
pyroptosis,
alkaliptosis,
oxeiptosis,
parthanatos,
mitochondrial
permeability
transition
(MPT)-driven
necrosis,
entotic
NETotic
lysosome-dependent
immunogenic
(ICD).
Furthermore,
focused
on
discussing
related
compounds.
brief,
insightful
findings
may
provide
valuable
guidance
investigating
individual
collaborative
approaches
towards
different
ultimately
driving
discovery
target
significantly
enhance
future
therapeutics.
Journal of Experimental & Clinical Cancer Research,
Год журнала:
2024,
Номер
43(1)
Опубликована: Ноя. 30, 2024
Abstract
Ferroptosis
is
a
type
of
regulated
cell
death
characterized
by
its
non-apoptotic,
iron-dependent
and
oxidative
nature.
Since
discovery
in
2012,
extensive
research
has
demonstrated
pivotal
roles
tumorigenesis,
metastasis
cancer
therapy.
The
tumor
microenvironment
(TME)
complex
ecosystem
comprising
cells,
non-cancer
extracellular
matrix,
metabolites
cytokines.
Recent
studies
have
underscored
new
paradigm
which
cells
the
TME,
such
as
immune
stromal
also
play
significant
regulating
progression
therapeutic
resistance
typically
through
complicated
crosstalk
with
cells.
Notably,
this
TME
were
partially
mediated
ferrotopsis-related
mechanisms.
This
review
provides
comprehensive
systematic
summary
current
findings
concerning
ferroptosis
how
ferroptosis-mediated
reprogramming
impacts
progression.
Additionally,
outlines
various
ferroptosis-related
strategies
aimed
at
targeting
TME.
Free Radical Biology and Medicine,
Год журнала:
2025,
Номер
228, С. 319 - 328
Опубликована: Янв. 7, 2025
Enzymatically
formed
side-chain
oxysterols
function
as
signaling
molecules
regulating
cholesterol
homeostasis
and
act
intermediates
in
the
biosynthesis
of
bile
acids.
In
addition
to
these
physiological
functions,
an
imbalance
oxysterol
has
been
implicated
pathophysiology.
Cholesterol
25-hydroxylase
(CH25H)
its
product
25-hydroxycholesterol
(25-OHC),
also
by
autoxidation,
are
associated
with
amyotrophic
lateral
sclerosis.
However,
effects
25-OHC
on
cell
viability
glial
cells
remain
unclear.
This
study
demonstrates
that
induces
ferroptosis,
iron-dependent
programmed
death,
mouse
Schwann
IMS32
cells.
Mechanistically,
suppressed
expression
selenoprotein
glutathione
peroxidase
4
(GPX4)
at
both
transcriptional
translational
levels
inhibiting
processing
sterol
regulatory
element-binding
proteins
(SREBPs).
addition,
upregulated
NADH-cytochrome
b5
reductase
1
(CYB5R1)
NADPH-cytochrome
P450
(POR),
enzymes
promote
lipid
peroxidation.
We
further
found
increases
glutathione-specific
gamma-glutamylcyclotransferase
(CHAC1)
decreases
levels.
Importantly,
non-cytotoxic
concentrations
enhanced
cellular
sensitivity
ferroptosis
inducers
downregulating
GPX4
expression.
These
findings
reveal
a
multifaceted
approach
whereby
through
SREBP
pathway
suppression
redox
Pharmaceuticals,
Год журнала:
2025,
Номер
18(3), С. 374 - 374
Опубликована: Март 6, 2025
Introduction:
Non-small
cell
lung
cancer
(NSCLC)
is
a
lethal
type
of
(LC)
with
5-year
survival
rate
19%.
Because
drug
resistance
typically
develops
following
chemotherapy,
radiotherapy,
and
immunotherapy,
novel
NSCLC
therapeutic
strategy
urgently
demanded.
Gambogenic
acid
(GNA),
major
bioactive
ingredient
isolated
from
gamboge,
has
multipotent
antitumor
effects,
although
activity
against
unknown.
Methods:
CCK8,
ethynyl
deoxyuridine
(EdU),
the
plate
colony
formation
assay,
transwell
wound
healing
(WH)
assay
were
used
to
study
effect
GNA
on
proliferation
migration
ability
NSCLC.
Flow
cytometry
was
detect
apoptosis
cycle.
Proteomic
analysis
LiP-SMap
downstream
target
GNA.
Ferroptosis
inhibitor
ferrostatin-1
ferroptosis.
Overexpressing
GCH1
for
rescue
experiment.
Subcutaneous
tumor
pulmonary
metastasis
in
mouse
model
growth
metastasis.
Results:
The
results
present
showed
that
inhibited
cells
dose-
time-dependent
manner,
which
arrested
cycle
G0/G1
phase.
In
vivo
data
revealed
found
significantly
expression
GTP
cyclohydrolase
1
(GCH1).
interacted
ILE248
ARG249
GCH1.
overexpression
had
similar
role
ferroptosis
restored
after
treatment.
Also,
promoted
reactive
oxygen
species
(ROS)
accumulation,
reduced
mitochondrial
membrane
potential.
or
treatment
reversed
regulation
ROS
accumulation
potential
inhibition.
Conclusions:
Taken
together,
these
findings
confirmed
suppressed
malignant
progression
by
inducing
GCH1-mediated
