Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Jan. 25, 2024
The
tryptophan-degrading
enzyme
indoleamine
2,3-dioxygenase
1
(IDO1)
is
a
plastic
immune
checkpoint
molecule
that
potently
orchestrates
responses
within
the
tumor
microenvironment
(TME).
As
heme-containing
protein,
IDO1
catalyzes
conversion
of
essential
amino
acid
tryptophan
into
immunoactive
metabolites,
called
kynurenines.
By
depleting
and
enriching
TME
with
kynurenines,
catalytic
activity
shapes
an
immunosuppressive
TME.
Accordingly,
inducible
or
constitutive
expression
in
cancer
correlates
negative
prognosis
for
patients,
representing
one
critical
tumor-escape
mechanisms.
However,
clinically
trialed
inhibitors
disappointed
expected
anti-tumor
efficacy.
Interestingly,
non-enzymatic
apo-form
still
active
as
transducing
capable
promoting
immunoregulatory
phenotype
dendritic
cells
(DCs)
well
pro-tumorigenic
behavior
murine
melanoma.
Moreover,
inhibitor
epacadostat
can
induce
tolerogenic
plasmacytoid
DCs,
overcoming
inhibition
IDO1.
Based
on
this
recent
evidence,
plasticity
was
investigated
human
ovarian
cell
line,
SKOV-3,
constitutively
expresses
dynamic
balance
between
holo-
apo-protein,
thus
potentially
endowed
dual
function
(i.e.,
enzymatic
non-enzymatic).
Besides
inhibiting
activity,
persistently
stabilizes
favoring
its
tyrosine-phosphorylation
association
phosphatase
SHP-2.
In
SKOV-3
cells,
both
these
early
molecular
events
activate
signaling
pathway
transduced
by
which
independent
contributes
to
tumorigenic
cells.
Overall,
our
findings
unveiled
new
mechanism
action
target,
repositioning
stabilizer
IDO1,
tumor.
This
could
contribute
clarify
lack
effectiveness
clinical
trials
shed
light
innovative
immunotherapeutic
strategies
tackle
target.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: March 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.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: March 22, 2023
Abstract
Tumour
cells
have
exquisite
flexibility
in
reprogramming
their
metabolism
order
to
support
tumour
initiation,
progression,
metastasis
and
resistance
therapies.
These
reprogrammed
activities
include
a
complete
rewiring
of
the
bioenergetic,
biosynthetic
redox
status
sustain
increased
energetic
demand
cells.
Over
last
decades,
cancer
field
has
seen
an
explosion
new
biochemical
technologies
giving
more
tools
than
ever
before
navigate
this
complexity.
Within
cell
or
tissue,
metabolites
constitute
direct
signature
molecular
phenotype
thus
profiling
concrete
clinical
applications
oncology.
Metabolomics
fluxomics,
are
key
technological
approaches
that
mainly
revolutionized
enabling
researchers
both
qualitative
mechanistic
model
cancer.
Furthermore,
upgrade
from
bulk
single-cell
analysis
provided
unprecedented
opportunity
investigate
biology
at
cellular
resolution
allowing
depth
quantitative
complex
heterogenous
diseases.
More
recently,
advent
functional
genomic
screening
allowed
identification
pathways,
processes,
biomarkers
novel
therapeutic
targets
concert
with
other
allow
patient
stratification
treatment
regimens.
This
review
is
intended
be
guide
for
metabolism,
highlighting
current
emerging
technologies,
emphasizing
advantages,
disadvantages
potential
leading
development
innovative
anti-cancer
Experimental & Molecular Medicine,
Journal Year:
2023,
Volume and Issue:
55(7), P. 1371 - 1379
Published: July 3, 2023
Amino
acids
are
fundamental
units
of
molecular
components
that
essential
for
sustaining
life;
however,
their
metabolism
is
closely
interconnected
to
the
control
systems
cell
function.
Tryptophan
(Trp)
an
amino
acid
catabolized
by
complex
metabolic
pathways.
Several
resulting
Trp
metabolites
bioactive
and
play
central
roles
in
physiology
pathophysiology.
Additionally,
various
physiological
functions
mutually
regulated
gut
microbiota
intestine
coordinately
maintain
intestinal
homeostasis
symbiosis
under
steady
state
conditions
during
immune
response
pathogens
xenotoxins.
Cancer
inflammatory
diseases
associated
with
dysbiosis-
host-related
aberrant
inactivation
aryl
hydrocarbon
receptor
(AHR),
which
a
several
metabolites.
In
this
review,
we
focus
on
mechanisms
through
converges
AHR
activation
modulation
function
restoration
tissue
how
these
processes
can
be
targeted
using
therapeutic
approaches
cancer
autoimmune
diseases.
Advanced Science,
Journal Year:
2023,
Volume and Issue:
10(6)
Published: Jan. 10, 2023
Abstract
Emerging
evidence
reveals
that
amino
acid
metabolism
plays
an
important
role
in
ferroptotic
cell
death.
The
conversion
of
methionine
to
cysteine
is
well
known
protect
tumour
cells
from
ferroptosis
upon
starvation
through
transamination.
However,
whether
acids‐produced
metabolites
participate
independent
the
pathway
largely
unknown.
Here,
authors
show
tryptophan
serotonin
(5‐HT)
and
3‐hydroxyanthranilic
(3‐HA)
remarkably
facilitate
escape
distinct
cysteine‐mediated
inhibition.
Mechanistically,
both
5‐HT
3‐HA
act
as
potent
radical
trapping
antioxidants
(RTA)
eliminate
lipid
peroxidation,
thereby
inhibiting
Monoamine
oxidase
A
(MAOA)
markedly
abrogates
protective
effect
via
degrading
5‐HT.
Deficiency
MAOA
renders
cancer
resistant
treatment.
Kynureninase
(KYNU),
which
essential
for
production,
confers
death,
whereas
3‐hydroxyanthranilate
3,4‐dioxygenase
(HAAO)
significantly
blocks
mediated
inhibition
by
consuming
3‐HA.
In
addition,
expression
level
HAAO
positively
correlated
with
peroxidation
clinical
outcome.
Together,
findings
demonstrate
works
a
new
anti‐ferroptotic
promote
growth,
targeting
this
will
be
promising
therapeutic
approach
Redox Biology,
Journal Year:
2024,
Volume and Issue:
69, P. 103030 - 103030
Published: Jan. 3, 2024
Ferroptosis
is
a
type
of
programmed
cell
death
resulting
from
iron
overload-dependent
lipid
peroxidation,
and
could
be
promoted
by
activating
transcription
factor
3
(ATF3).
SIRT1
an
enzyme
accounting
for
removing
acetylated
lysine
residues
target
proteins
consuming
NAD+,
but
its
role
remains
elusive
in
ferroptosis
ATF3.
In
this
study,
we
found
was
activated
during
the
process
RSL3-induced
glioma
ferroptosis.
Moreover,
aggravated
activator
SRT2183,
suppressed
SIRT
inhibitor
EX527
or
when
silenced
with
siRNA.
These
indicated
sensitized
cells
to
Furthermore,
expressional
upregulation
nuclear
translocation
Silence
ATF3
siRNA
attenuated
increases
ferrous
downregulation
SLC7A11
GPX4
depletion
cysteine
GSH.
Thus,
inducting
activation.
Mechanistically,
activation
reinforced
decline
NAD+
FK866
that
inhibit
NAD
+
synthesis
via
salvage
pathway,
intracellular
maintained
at
higher
level
supplement
exogenous
NAD+.
Notably,
caused
RSL3
enhanced
further
inhibited
EX527.
consumption
Finally,
inducing
reactive
oxygen
species-dependent
AROS.
Together,
our
study
revealed
AROS
sensitizes
ATF3-dependent
inhibition
GPX4.
Journal of Cellular and Molecular Medicine,
Journal Year:
2025,
Volume and Issue:
29(2)
Published: Jan. 1, 2025
Postmenopausal
osteoporosis
(PMOP)
is
a
chronic
systemic
bone
metabolism
disorder.
Promotion
in
the
patterns
of
human
marrow
mesenchymal
stem
cells
(hBMSCs)
differentiation
towards
osteoblasts
contributes
to
alleviating
osteoporosis.
Aucubin,
natural
compound
isolated
from
well-known
herbal
medicine
Eucommia,
was
previously
shown
possess
various
pharmacological
effects.
However,
its
effects
on
hBMSCs
PMOP
patients
are
unknown.
The
aim
this
present
research
investigate
impact
and
underlying
process
aucubin
cell
proliferation
osteogenic
patients.
ability
inhibit
ferroptosis
induced
by
erastin
detected;
ROS
production,
ferrous
ion
levels,
SOD,
MDA,
GPX
activities
were
tested
using
commercial
kits.
Next,
ALP
staining,
ARS
RT-qPCR,
RNA-sequencing,
Western
blot
applied
for
determining
mRNA
protein
expression
levels
associated
with
osteogenesis
hBMSCs.
study
also
explored
involvement
BMP2/Smads
signalling
promoting
evaluated
intervention
an
ovariectomised
rat
model.
results
indicated
that
significantly
inhibited
generation
oxidative
stress
protected
against
Additionally,
facilitated
activating
BMP2/SMADs
pathway
attenuated
progression
OVX
rats,
suggesting
potential
therapeutic
benefit
postmenopausal
(PMOP).
Frontiers in Oncology,
Journal Year:
2025,
Volume and Issue:
14
Published: Jan. 22, 2025
The
pivotal
role
of
metabolic
reprogramming
in
cancer-related
drug
resistance,
through
the
tryptophan-catabolized
kynurenine
pathway
(KP),
has
been
particularly
underscored
recent
research.
This
pathway,
driven
by
indoleamine
2,3-dioxygenase
1
(IDO1),
facilitates
immune
evasion
and
promotes
tumor
progression
fostering
an
immunosuppressive
environment.
In
Phase
III
investigation
combination
IDO1
inhibition
with
checkpoint
inhibitors
(ICIs),
therapy
was
not
efficacious.
this
review,
we
revisit
current
advances,
explore
future
directions,
emphasize
importance
dual
KP
rate-limiting
enzymes
tryptophan
2,3-dioxygenase-2
(TDO2)
appropriate
patient
populations.
We
propose
that
may
maximize
therapeutic
potential
inhibition.
Additionally,
delve
into
complex
cellular
interactions
cancer
dependencies
within
microenvironment
(TME).
Insights
from
preclinical
studies,
clinical
trials,
promising
combinations
will
be
discussed
to
elucidate
promote
a
clear
path
forward
for
direction
research
outcomes.