Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 16, 2024
The
emerged
apoptosis/ferroptosis
synergistic
platinum-based
therapy
has
attracted
a
lot
of
attention
but
is
far
from
clinic
use
due
to
high
systemic
toxicity.
Herein,
series
novel
precise
carrier-free
self-assembled
platinum(IV)
nanoparticles
with
lipid
regulation
effect
named
FSPNPs
(5NPs–8NPs)
were
constructed
via
connecting
fenofibrate
acid
(FA)
cisplatin
or
oxaliplatin-derived
platinum(IV)-intermediates
disulfide
bonds.
can
be
stimulated
by
high-glutathione/ascorbic
and
acidity
environment
produce
an
"explosion-like"
cascade
release
process.
Cell-activity
showed
precision
FSPNPs,
which
accumulated
more
in
tumor
cells
inhibited
cell
proliferation.
Especially,
5NPs
have
higher
selectivity
than
cisplatin.
downregulated
glutathione/glutathione
peroxidase
4,
increased
reactive
oxygen
species/lipid
peroxidation/malondialdehyde,
induced
DNA
damage/S-phase
arrest,
regulated
p53/Bcl-2/Bax
trigger
the
hybrid
pathway.
released
FA
derivates
docked
into
peroxisome
proliferator-activated
receptor
α
activating
cholesterol
metabolism
destroy
membrane
integrity.
also
good
biocompatibility
superior
antitumor
activity
no
observable
tissue
damage.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Май 23, 2024
Ferroptosis
is
a
non-apoptotic
mode
of
programmed
cell
death
characterized
by
iron
dependence
and
lipid
peroxidation.
Since
the
ferroptosis
was
proposed,
researchers
have
revealed
mechanisms
its
formation
continue
to
explore
effective
inhibitors
in
disease.
Recent
studies
shown
correlation
between
pathological
neurodegenerative
diseases,
as
well
diseases
involving
tissue
or
organ
damage.
Acting
on
ferroptosis-related
targets
may
provide
new
strategies
for
treatment
ferroptosis-mediated
diseases.
This
article
specifically
describes
metabolic
pathways
summarizes
reported
action
natural
synthetic
small
molecule
their
efficacy
The
paper
also
treatments
such
gene
therapy,
nanotechnology,
summarises
challenges
encountered
clinical
translation
inhibitors.
Finally,
relationship
other
modes
discussed,
hopefully
paving
way
future
drug
design
discovery.
Ferroptosis
is
a
nonapoptotic
form
of
cell
death
characterized
by
iron-dependent
lipid
peroxidation
in
membrane
phospholipids.
Since
its
identification
2012,
extensive
research
has
unveiled
involvement
the
pathophysiology
numerous
diseases,
including
cancers,
neurodegenerative
disorders,
organ
injuries,
infectious
autoimmune
conditions,
metabolic
and
skin
diseases.
Oxidizable
lipids,
overload
iron,
compromised
antioxidant
systems
are
known
as
critical
prerequisites
for
driving
overwhelming
peroxidation,
ultimately
leading
to
plasma
rupture
ferroptotic
death.
However,
precise
regulatory
networks
governing
ferroptosis
ferroptosis-targeted
therapy
these
diseases
remain
largely
undefined,
hindering
development
pharmacological
agonists
antagonists.
In
this
review,
we
first
elucidate
core
mechanisms
summarize
epigenetic
modifications
(e.g.,
histone
modifications,
DNA
methylation,
noncoding
RNAs,
N6-methyladenosine
modification)
nonepigenetic
genetic
mutations,
transcriptional
regulation,
posttranslational
modifications).
We
then
discuss
association
between
disease
pathogenesis
explore
therapeutic
approaches
targeting
ferroptosis.
also
introduce
potential
clinical
monitoring
strategies
Finally,
put
forward
several
unresolved
issues
which
progress
needed
better
understand
hope
review
will
offer
promise
application
therapies
context
human
health
disease.
Phytomedicine,
Год журнала:
2025,
Номер
140, С. 156624 - 156624
Опубликована: Март 6, 2025
Doxorubicin
(Dox)-induced
cardiomyopathy
(DIC)
is
characterized
by
severe
myocardial
damage
that
can
progress
to
dilated
and
potentially
lead
heart
failure.
No
effective
prevention
or
treatment
strategies
are
available
for
DIC.
Sauchinone,
a
diastereomeric
lignan
isolated
from
Saururus
chinensis,
known
its
notable
anti-inflammatory
effects.
However,
paucity
of
research
on
sauchinone
in
relation
disease
exists,
particularly
regarding
role
DIC,
which
remains
unclear.
This
study
aimed
assess
the
therapeutic
potential
alleviating
cardiac
injury
elucidate
molecular
mechanism
Male
C57BL/6J
mice
were
used
construct
chronic
acute
DIC
models
vivo.
The
administered
intragastrically
concurrently
with
first
injection
Dox
evaluate
effect
H9c2,
rat
cardiomyocyte
cell
line,
was
treated
various
concentrations
conjunction
protective
effects
vitro.
Supplementation
exogenous
mitigated
Dox-induced
atrophy,
fibrosis,
ventricular
remodeling,
while
preserving
function.
Sauchinone
reduced
abnormal
apoptosis
both
vitro
Additionally,
restored
mitochondrial
function
decreased
reactive
oxygen
species
levels,
may
be
attributed
activation
nuclear
factor
erythroid
2-related
2
(NRF2)
signaling,
thereby
attenuating
oxidative
damage.
Furthermore,
significantly
inhibited
NOD-like
receptor
thermal
protein
domain
associated
3
(NLRP3)
inflammasome
infiltration
inflammatory
factors,
stress
inhibiting
progression
NLRP3
agonist
nigericin
abolished
progression,
antagonist
MCC950
further
enhanced
beneficial
vivo
key
novel
finding
present
use
sauchinone,
effectively
limits
Specifically,
not
only
alleviates
but
also
delays
Mechanistically,
inactivation
NRF2-mediated
antioxidant
pathways
have
been
identified
as
two
critical
signaling
regulated
plays
vital
blocking
holds
promise
approach
cardiomyopathy.
Conventional
androgen
deprivation
therapy
(ADT)
targets
the
receptor
(AR)
inhibiting
prostate
cancer
(PCa)
progression;
however,
it
can
eventually
lead
to
recurrence
as
castration-resistant
PCa
(CRPC),
which
has
high
mortality
rates
and
lacks
effective
treatment
modalities.
The
study
confirms
presence
of
glutathione
peroxidase
4
(GPX4)
expression,
a
key
regulator
ferroptosis
(i.e.,
iron-dependent
program
cell
death)
in
CRPC
cells.
Therefore,
inducing
cells
might
be
an
therapeutic
modality
for
CRPC.
However,
nonspecific
uptake
inducers
result
undesirable
cytotoxicity
major
organs.
Thus,
precisely
induce
cells,
genetic
engineering
strategy
is
proposed
embed
prostate-specific
membrane
antigen
(PSMA)-targeting
antibody
fragment
(gy1)
macrophage
membrane,
then
coated
onto
mesoporous
polydopamine
(MPDA)
nanoparticles
produce
biomimetic
nanoplatform.
results
indicate
that
membrane-coated
(MNPs)
exhibit
specificity
affinity
toward
On
further
encapsulation
with
RSL3
iron
ions,
MPDA/Fe/RSL3@M-gy1
demonstrates
superior
synergistic
effects
highly
targeted
eliciting
significant
efficacy
against
tumor
growth
bone
metastasis
without
increased
cytotoxicity.
In
conclusion,
new
reported
PSMA-specific,
CRPC-targeting
platform
induction
safety.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
179, С. 117312 - 117312
Опубликована: Авг. 20, 2024
Anthracyclines
are
broad-spectrum
anticancer
drugs,
but
their
clinical
use
is
limited
due
to
severe
cardiotoxicity.
Anthracycline-induced
cardiotoxicity
(AIC)
remains
a
significant
cause
of
heart
disease-related
mortality
in
many
cancer
survivors.
The
underlying
mechanisms
AIC
have
been
explored
over
the
past
few
decades.
Reactive
oxygen
species
and
drug-induced
inhibition
topoisomerase
II
beta
well-studied
mechanisms,
with
mitochondria
being
prominently
investigated
organelle.
Emerging
such
as
ferroptosis,
Ca
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
176, С. 116761 - 116761
Опубликована: Май 23, 2024
The
discovery
of
regulatory
cell
death
processes
has
driven
innovation
in
cardiovascular
disease
(CVD)
therapeutic
strategies.
Over
the
past
decade,
ferroptosis,
an
iron-dependent
form
regulated
by
excessive
lipid
peroxidation,
been
shown
to
drive
development
multiple
CVDs.
This
review
provides
insights
into
evolution
concept
similarities
and
differences
with
traditional
modes
programmed
(e.g.,
apoptosis,
autophagy,
necrosis),
as
well
core
mechanisms
ferroptosis
(including
cystine/glutamate
transporter
blockade,
imbalance
iron
metabolism,
peroxidation).
In
addition,
it
not
only
a
detailed
role
its
potential
widely
studied
CVDs
such
coronary
atherosclerotic
heart
disease,
myocardial
infarction,
ischemia/reperfusion
injury,
failure,
cardiomyopathy,
aortic
aneurysm
but
also
overview
phenomenon
perspectives
lesser-addressed
cardiac
valvulopathy,
pulmonary
hypertension,
sickle
disease.
article
aims
integrate
this
knowledge
provide
comprehensive
view
wide
range
progress
strategies
field.
Aberrant
lipid
metabolism
is
a
well-recognized
hallmark
of
cancer.
Notably,
breast
cancer
(BC)
arises
from
lipid-rich
microenvironment
and
depends
significantly
on
metabolic
reprogramming
to
fulfill
its
developmental
requirements.
In
this
review,
we
revisit
the
pivotal
role
in
BC,
underscoring
impact
progression
tumor
microenvironment.
Firstly,
delineate
overall
landscape
highlighting
roles
patient
prognosis.
Given
that
lipids
can
also
act
as
signaling
molecules,
next
describe
exchanges
between
BC
cells
other
cellular
components
Additionally,
summarize
therapeutic
potential
targeting
aspects
processes,
lipid-related
transcription
factors
immunotherapy
BC.
Finally,
discuss
possibilities
problems
associated
with
clinical
applications
lipid‑targeted
therapy
propose
new
research
directions
advances
spatiotemporal
multi-omics.
