Exploring the Mechanism of Ferroptosis Induction by Sappanone A in Cancer: Insights into the Mitochondrial Dysfunction Mediated by NRF2/xCT/GPX4 Axis
Junyan Wang,
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Haowen Zhuang,
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Xiaocui Yang
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et al.
International Journal of Biological Sciences,
Journal Year:
2024,
Volume and Issue:
20(13), P. 5145 - 5161
Published: Jan. 1, 2024
Non-small
cell
lung
cancer
(NSCLC),
a
major
subtype
of
cancer,
encompasses
squamous
carcinoma,
adenocarcinoma,
and
large
carcinoma.
Compared
to
small
NSCLC
cells
grow
divide
more
slowly,
their
metastasis
occurs
at
later
stage.
Currently,
chemotherapy
is
the
primary
treatment
for
this
disease.
Sappanone
A
(SA)
flavonoid
compound
extracted
from
plant
Caesalpinia
sappan,
known
its
antitumor,
redox-regulating,
anti-inflammatory
properties.
Recent
studies
have
investigated
interaction
SA
with
mitochondrial
pathways
in
regulating
death
through
Nrf-2/GPX-4/xCT
axis.
This
study
specifically
explores
mechanism
by
which
affects
morphology
structure
regulation
mitophagy
biogenesis
tumor
cells.
The
primarily
utilizes
second-generation
transcriptomic
sequencing
data
molecular
docking
techniques
elucidate
role
programmed
omics
results
indicate
that
significantly
targets
genes
involved
oxidative
phosphorylation,
mitophagy,
dynamics,
stress.
Further
findings
confirmed
Nrf-2/GPX4/xCT
pathway
serves
as
crucial
target
NSCLC.
Knockdown
Nrf-2
(si-Nrf-2)
overexpression
(ad-Nrf-2)
were
shown
modulate
therapeutic
efficacy
varying
degrees.
Additionally,
modifications
GPX4/xCT
affected
regulatory
effects
on
autophagy,
biogenesis,
energy
metabolism.
These
mechanisms
may
be
mediated
caspase
ferroptosis-related
signaling.
Molecular
biology
experiments
demonstrated
intervention
further
inhibits
phosphorylation
FUNDC1
Tyr18
downregulates
TOM20
expression.
was
found
reduce
expression
PGC1α,
Nrf-1,
Tfam,
resulting
decrease
respiration
Overexpression
counteract
biogenesis.
Confocal
microscopy
revealed
increases
fragmentation,
subsequently
inducing
pathway-mediated
death.
However,
genetic
modification
altered
In
conclusion,
has
been
identified
promising
agent
apoptosis
ferroptosis
represent
key
Targeting
axis
offers
novel
approach
maintaining
homeostasis
within
cellular
microenvironment.
Language: Английский
Exploring the Potential of Mitochondria‐Targeted Drug Delivery for Enhanced Breast Cancer Therapy
International Journal of Breast Cancer,
Journal Year:
2025,
Volume and Issue:
2025(1)
Published: Jan. 1, 2025
Breast
cancer
stands
as
the
utmost
prevalent
malignancy
in
women,
impacting
epithelial
tissue
of
breast
and
often
displaying
resistance
to
effective
treatment
due
its
diverse
molecular
histological
features.
Current
modalities
may
exhibit
decreasing
efficacy
over
time
can
lead
disease
progression.
The
mitochondria,
a
crucial
organelle
responsible
for
cellular
metabolism
energy
supply,
stand
highly
sensitive
both
heat
reactive
oxygen
species,
presenting
an
assuring
target
photodynamic
photothermal
therapies
(PTTs)
cure.
employment
nanodrug
carriers
combination
deliveries
holds
promise
addressing
challenges
related
drug
degradation
off-target
toxicity.
By
circumventing
reticuloendothelial
system,
nanocarriers
bolster
drug's
bioavailability
at
intended
site
ensure
controlled
codelivery
multiple
drugs,
thereby
maintaining
normal
pharmacokinetic
features
regular
pharmacodynamic
characteristics
different
therapeutic
mechanisms.
precision
this
innovative
technology
have
revolutionized
delivery,
substantially
enhancing
effectiveness.
In
pursuit
targeting
mitochondrial
modifications
cells,
various
such
therapy
(PDT),
PTT,
chemodynamic
(CDT)
been
explored.
These
improved
efficiency
mitochondria-targeted
their
advantageous
properties
minimal
toxicity,
noninvasiveness,
reduced
resistance,
safer
profile.
Our
review
article
provides
exhaustive
overview
alterations
environment
BC,
impact
on
BC
development,
potential
targets
treatment,
nanotherapeutic
approaches
limitations
these
approaches.
Language: Английский
Integrative Genomic and in Silico Analysis Reveals Mitochondrially Encoded Cytochrome C Oxidase III (MT—CO3) Overexpression and Potential Neem-Derived Inhibitors in Breast Cancer
Genes,
Journal Year:
2025,
Volume and Issue:
16(5), P. 546 - 546
Published: April 30, 2025
Background:
The
increasing
global
incidence
of
breast
cancer
calls
for
the
identification
new
therapeutic
targets
and
assessment
possible
neem-derived
inhibitors
by
means
computational
modeling
integrated
genomic
research.
Methods:
Originally
looking
at
59,424
genes
throughout
42
samples,
we
investigated
gene
expression
data
from
Cancer
Genome
Atlas—Breast
(TCGA-BRCA)
dataset.
We
chose
286
thorough
investigation
following
strict
screening
consistent
expression.
R’s
limma
package
was
used
in
differential
analysis.
leading
candidate’s
protein
done
with
Swiss-ADME
Discovery
Studio.
Molecular
docking
studies,
including
132
neem
compounds,
were
conducted
utilizing
AutoDock
Vina.
Results:
Among
examined,
mitochondrially
encoded
cytochrome
C
oxidase
III
(MT—CO3)
turned
out
to
be
most
greatly
overexpressed
gene,
showing
elevation
across
all
samples.
Protein
revealed
a
substantial
hydrophobic
pocket
(volume:
627.3
Å3)
inside
structure
MT—CO3.
Docking
investigations
showed
five
interesting
inhibitors:
7-benzoylnimbocinol,
nimolicinol,
melianodiol,
isonimocinolide,
stigmasterol.
Strong
binding
affinities
ranging
−9.2
−11.5
kcal/mol
diverse
interactions
MT—CO3,
mostly
involving
residues
Phe214,
Arg221,
Trp58,
these
molecules
displayed.
With
dominant
chemicals,
fragment
contribution
analysis
that
scaffold
percentage
influences
effectiveness.
Stigmasterol
greater
drug-likeness
(QED
=
0.79)
despite
minimal
interaction
variety,
while
7-benzoylnimbocinol
presented
best-balanced
physicochemical
profile.
Conclusion:
Connecting
traditional
medicine
current
genomics
biology,
this
work
proposes
methodology
structure-guided
drug
design
development
using
chemicals
finds
MT—CO3
as
potential
target
cancer.
Language: Английский
The Transformative Role of Nanoenzymes in the Diagnosis, Targeted Treatment, and Prognosis of Ovarian Cancer. A comprehensive review
Ahmed Imran,
No information about this author
Aqsa Gulzar,
No information about this author
Muhammad Rehman Gulzar
No information about this author
et al.
Developmental medico-life-sciences,
Journal Year:
2024,
Volume and Issue:
1(10), P. 4 - 22
Published: Dec. 13, 2024
Ovarian
cancer
is
one
of
the
most
aggressive
and
deadly
gynaecological
malignancies
remains
frequently
diagnosed
at
advanced
stages
because
its
asymptomatic
progression
inherent
limitations
current
diagnostic
tests.
Nanoenzymes
(a
class
nanotechnology-based
artificial
enzymes)
have
great
promise
in
addressing
these
challenges.
greatly
improve
sensitivity
specificity
biosensors
including
optical
electrochemical
systems,
with
real-time
high-precision
detection
key
biomarkers
such
as
CA-125,
HE4,
mesothelin.
The
high
accuracy
biosensors,
fluorescence
surface
plasmon
resonance
(SPR)
based
technologies,
for
early-stage
diagnosis,
cost-effective,
portable,
ultra-low
limits
make
them
attractive
alternatives.
Nanoenzyme-based
drug
delivery
systems
like
liposomes,
polymeric
micelles,
Nanocapsules
therapeutic
outcomes
by
allowing
targeted
transport
to
tumor
tissues,
reducing
systemic
toxicity,
overcoming
resistance
treatment.
PEGylated
liposomal
doxorubicin
(Doxil),
a
formulation,
has
been
shown
enhanced
efficacy
platinum-resistant
ovarian
cancer,
reduced
adverse
effects.
Further
theranostic
applications
metallic
nanoparticles
gold
iron
oxide
can
be
realized
using
therapy
imaging.
These
advancements
come
their
challenges,
however,
biological
barriers,
scalability
before
clinical
translation.
Interdisciplinary
research,
validation,
creation
regulatory
frameworks
safety
are
needed
future
progress.
offer
revolutionize
diagnosis
treatment
potential
facilitate
early
detection,
precision,
patient
outcome
while
filling
huge
gaps
approaches.
Language: Английский