A novel small molecule NJH-13 induces pyroptosis via the Ca2+ driven AKT-FOXO1-GSDME signaling pathway in NSCLC by targeting TRPV5
Journal of Advanced Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Pyroptosis
represents
a
mode
of
programmed
necrotic
cell
death
(PCD),
mediated
by
members
gasdermin
family
(GSDMs),
such
as
GSDME.
It
is
emerging
promising
approach
for
combating
cancer.
Notably,
GSDME
the
key
modulator
switch
between
apoptosis
and
pyroptosis
in
cells.
However,
often
downregulated
many
malignancies,
including
lung
adenocarcinoma.
To
identify
novel
inducers
non-small
cancer
(NSCLC)
dissect
underlying
mechanism.
was
examined
live
imaging,
PI/Hoechst/Annexin
V
staining,
LDH
release
assay,
ELISA,
western
blot
assays.
DARTS,
CETSA,
molecular
docking
used
to
target
NJH-13.
RNA-seq,
qPCR,
chromatin
immunoprecipitation
(ChIP),
dual
luciferase
assays
were
elucidate
In
this
study,
NJH-13,
an
N-containing
heterocycle,
screened
out
identified
possess
ability
activate
GSDME,
consequently
triggering
NSCLC
By
using
DARTS
strategy,
transient
receptor
potential
cation
channel
subfamily
member
5
(TRPV5)
NJH-13
increased
intracellular
calcium
level
triggered
oxidative
stress,
both
which
are
critical
events
leading
Mechanistically,
enhanced
transcription
via
protein
kinase
B
(AKT)/forkhead
box
factor
O1
(FOXO1)
signaling
pathway.
ChIP
revealed
that
FOXO1
bound
directly
promoter
region
thus
GSDME-mediated
pyroptosis.
Pharmacological
genetic
activation
AKT
or
inhibition
partially
rescued
NJH-13-induced
pyroptotic
death.
Moreover,
treatment
suppressed
tumor
growth
vivo.
Taken
together,
our
results
TRPV5
distinctive
manipulating
provided
evidence
functions
anti-cancer
agent
capable
Язык: Английский
Exploring mechanisms of skin aging: insights for clinical treatment
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Ноя. 8, 2024
The
skin
is
the
largest
organ
in
human
body
and
made
up
of
various
cells
structures.
Over
time,
will
age,
which
not
only
influenced
by
internal
factors,
but
also
external
environmental
especially
ultraviolet
radiation.
Aging
causes
immune
system
weakening
elderly,
makes
them
more
susceptible
to
dermatosis,
such
as
type
2
inflammatory
mediated
pruritus.
response
this
condition
marked
senescent
consistently
releasing
low
amounts
pro-inflammatory
cytokines
through
a
senescence-associated
secretory
phenotype
(SASP).
This
continuous
inflammation
may
accelerate
aging
establish
connection
between
diseases.
In
addition,
two
chronic
pigmentation
disorders,
vitiligo
chloasma,
are
associated
with
aging.
Aged
escape
accumulate
tissues,
forming
microenvironment
that
promotes
cancer.
At
same
"photoaging"
caused
excessive
exposure
radiation
an
important
cause
manuscript
describes
possible
links
inflammation,
cancer
suggests
some
treatment
options.
Язык: Английский
Unveiling ferroptosis: a new frontier in skin disease research
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Окт. 4, 2024
Ferroptosis,
a
form
of
regulated
cell
death
distinct
from
apoptosis,
necrosis,
and
autophagy,
is
increasingly
recognized
for
its
role
in
skin
disease
pathology.
Characterized
by
iron
accumulation
lipid
peroxidation,
ferroptosis
has
been
implicated
the
progression
various
conditions,
including
psoriasis,
photosensitive
dermatitis,
melanoma.
This
review
provides
an
in-depth
analysis
molecular
mechanisms
underlying
compares
cellular
effects
with
other
forms
context
health
disease.
We
systematically
examine
five
specific
diseases,
ichthyosis,
polymorphous
light
eruption
(PMLE),
vitiligo,
melanoma,
detailing
influence
on
pathogenesis
progression.
Moreover,
we
explore
current
clinical
landscape
ferroptosis-targeted
therapies,
discussing
their
potential
managing
treating
diseases.
Our
aim
to
shed
therapeutic
modulating
research
practice.
Язык: Английский