Journal of Biological Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown, P. 108473 - 108473
Published: April 1, 2025
Tissue
inhibitor
of
metalloproteinase
1
(TIMP1)
has
been
implicated
in
prostate
cancer
metastasis.
In
this
study,
PC-3M-2B4
cells
with
TIMP1
knockdown
(PC-3M-2B4-shTIMP1)
or
over-expression
(PC-3M-2B4-TIMP1)
were
generated
and
an
inverse
correlation
was
found
between
expression
cell
migration
invasion
which
confirmed
vitro
vivo.
Differential
accompanied
by
variations
the
ferroptosis-related
proteins,
glutathione
peroxidase
4
(GPX4),
transferrin
receptor
(TFRC),
(TF),
glutamine
cysteine
ligase
catalytic
subunit
(GCLC)
modifier
(GCLM).
comparison
TIMP1-overexpressing
cells,
TIMP1-knockdown
demonstrated
a
12.3%
decrease
Fe2+
concentration
after
erastin
treatment,
37.8%
reduction
malondialdehyde
(MDA)
levels,
113.7%
increase
GPX4
expression,
78.9%
rise
GSH/GSSG
ratio.
Our
findings
indicate
that
overexpression
promotes
ferroptosis
modulating
critical
markers
such
as
TFRC,
thereby
significantly
reducing
metastatic
potential
cells.
results
highlight
TIMP1's
role
regulating
pathways,
are
crucial
for
tumor
progression,
exposes
therapeutic
target
management.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: March 11, 2025
Ferroptosis,
an
iron-dependent
form
of
regulated
cell
death
driven
by
lipid
peroxidation,
plays
a
pivotal
role
in
various
physiological
and
pathological
processes.
In
this
review,
we
summarize
the
core
mechanisms
ferroptosis,
emphasizing
its
intricate
connections
to
metabolism,
including
fatty
acid
synthesis,
phospholipid
remodeling,
oxidation
dynamics.
We
further
highlight
advancements
detection
technologies,
such
as
fluorescence
imaging,
lipidomics,
vivo
PET
which
have
deepened
our
understanding
ferroptotic
regulation.
Additionally,
discuss
ferroptosis
human
diseases,
where
it
acts
double-edged
sword,
contributing
cancer
while
also
driving
ischemia-reperfusion
injury
neurodegeneration.
Finally,
explore
therapeutic
strategies
aimed
at
either
inducing
or
inhibiting
iron
chelation,
antioxidant
modulation,
lipid-targeted
interventions.
By
integrating
mechanistic
insights,
disease
relevance,
potential,
review
provides
comprehensive
perspective
on
crucial
interface
between
metabolism
oxidative
stress.
Antioxidants,
Journal Year:
2025,
Volume and Issue:
14(4), P. 412 - 412
Published: March 29, 2025
Curcumin
is
recognized
for
its
diverse
biological
activities,
including
the
ability
to
induce
apoptosis
and
ferroptosis.
Therefore,
it
represents
a
promising
candidate
development
of
new
compounds
with
neuroprotective
anticancer
properties.
In
order
synthesize
mimics
improved
pharmacokinetic
properties
(better
solubility
stability
than
curcumin)
here,
we
present
design
synthesis
novel
curcumin
analogues
named
Ethylphosphonate-based
(EPs),
which
preserve
pharmacophoric
features
curcumin.
New
EP
were
synthesized
by
tyrosol-
melatonin-based
building
blocks
using
an
orthogonal
protection
approach
different
precursors’
OH
functions
good
yields
in
few
steps.
Comparative
screenings
cytotoxic
cytoprotective
(curcumin
was
used
as
reference
compound)
carried
out
on
all
cell
lines
(HeLa,
A375,
WM266,
MDA-MB-231,
LX2,
HDF).
Assays
inhibitors
ferroptosis
(Ferrostatin-1,
Fer-1)
(Quinoline-Val-Asp-difluorophenoxymethyl
ketone,
Q-VD),
combination
curcumin,
suggested
specific
death
pathway
(apoptotic
or
ferroptotic)
EPs,
depending
aromatic
moieties
contained
them.
Interestingly,
EP4
exhibited
substantial
effects
against
various
human
cancer
WM266)
while
sparing
normal
cells
(HDFs).
displayed
five-times-higher
toxicity
triple-negative
MDA-MB-231
LX2
stellate
The
cytotoxicity
exerted
involves
only
apoptotic
mechanism,
contrary
exerts
both
ferroptotic
effects.
Additionally,
also
found
be
very
potent
inhibitor
ubiquitin-activating
enzyme
E1,
reinforcing
potential
this
compound.
Furthermore,
EP2
possesses
high
antioxidant
properties,
efficiently
protects
ferroptosis,
inhibits
amyloid
aggregation
involved
AD.
Journal of Biological Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown, P. 108473 - 108473
Published: April 1, 2025
Tissue
inhibitor
of
metalloproteinase
1
(TIMP1)
has
been
implicated
in
prostate
cancer
metastasis.
In
this
study,
PC-3M-2B4
cells
with
TIMP1
knockdown
(PC-3M-2B4-shTIMP1)
or
over-expression
(PC-3M-2B4-TIMP1)
were
generated
and
an
inverse
correlation
was
found
between
expression
cell
migration
invasion
which
confirmed
vitro
vivo.
Differential
accompanied
by
variations
the
ferroptosis-related
proteins,
glutathione
peroxidase
4
(GPX4),
transferrin
receptor
(TFRC),
(TF),
glutamine
cysteine
ligase
catalytic
subunit
(GCLC)
modifier
(GCLM).
comparison
TIMP1-overexpressing
cells,
TIMP1-knockdown
demonstrated
a
12.3%
decrease
Fe2+
concentration
after
erastin
treatment,
37.8%
reduction
malondialdehyde
(MDA)
levels,
113.7%
increase
GPX4
expression,
78.9%
rise
GSH/GSSG
ratio.
Our
findings
indicate
that
overexpression
promotes
ferroptosis
modulating
critical
markers
such
as
TFRC,
thereby
significantly
reducing
metastatic
potential
cells.
results
highlight
TIMP1's
role
regulating
pathways,
are
crucial
for
tumor
progression,
exposes
therapeutic
target
management.
