Dehydrodiisoeugenol targets the PLK1-p53 axis to inhibit breast cancer cell cycle
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 28, 2025
Introduction
There
are
about
2,300,000
new
cases
of
breast
cancer
worldwide
each
year.
Breast
has
become
the
first
most
common
in
world
and
leading
cause
death
among
women.
At
same
time,
chemotherapy
resistance
patients
with
advanced
is
still
a
serious
challenge.
Alpinia
Katsumadai
Hayata
(AKH),
as
traditional
Chinese
herbal
medicine,
wide
range
pharmacological
activities.
Related
studies
have
found
that
many
compounds
AKH
anti-breast
activity.
However,
it
worth
exploring
which
component
main
active
inhibiting
its
mechanism
action.
Methods
In
this
study,
dehydrodiisoeugenol
(DHIE)
was
screened
ingredient
against
based
on
LC-MS
combined
drug
similarity
disease
enrichment
analysis.
WGCNA,
network
pharmacology,
molecular
docking,
transcriptome
sequencing
analysis,
immune
infiltration
analysis
single-cell
were
used
to
explore
DHIE
cancer.
CCK-8,
flow
cytometry
Western
blot
verify
results
vitro
.
The
efficacy
drugs
verified
vivo
by
constructing
subcutaneous
tumor-bearing
mouse
model.
Results
Our
research
showed
enriched
core
gene
targets
mainly
act
epithelial
cells
tissues
significantly
inhibit
growth
affecting
PLK1-p53
signaling
axis
arrest
cell
cycle
at
G0/G1
phase.
Further
although
had
opposite
regulatory
effects
different
isoforms
p53
types
cells,
they
eventually
caused
arrest.
addition,
reduced
tumor
burden,
level
proliferation-related
marker
Ki-67,
inhibited
expression
PLK1
model,
further
enhanced
when
DOX.
Discussion
Collectively,
our
study
suggests
AHK
may
induce
regulating
axis,
provide
therapeutic
strategy
for
specific
mechanisms
regulates
subtypes
advantages
chemotherapeutic
combinations
compared
other
exploring.
Language: Английский
Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons
Cancer Reports,
Journal Year:
2024,
Volume and Issue:
7(4)
Published: April 1, 2024
Abstract
Background
Iatrogenesis
is
an
inevitable
global
threat
to
healthcare
that
drastically
increases
morbidity
and
mortality.
Cancer
a
fatal
pathological
condition
affects
people
of
different
ages,
sexes,
races
around
the
world.
In
addition
detrimental
cancer
pathology,
one
most
common
contraindications
challenges
observed
in
patients
severe
adverse
drug
effects
hypersensitivity
reactions
induced
by
chemotherapy.
Chemotherapy‐induced
cognitive
neurotoxicity
clinically
referred
as
impairment
(CICI),
chemobrain,
or
chemofog.
CICI,
chemotherapy
also
causes
neuropsychiatric
issues,
mental
disorders,
hyperarousal
states,
movement
disorders.
A
synergistic
regimen
Doxorubicin
(Anthracycline‐DOX)
Cyclophosphamide
(Alkylating
Cytophosphane‐CPS)
indicated
for
management
various
cancers
(breast
cancer,
lymphoma,
leukemia).
Nevertheless,
there
are
limited
research
studies
on
Cyclophosphamide's
pharmacodynamic
toxicological
dopaminergic
neuronal
function.
Aim
This
study
evaluated
neurotoxic
Cyclophosphamide.
Methods
Results
were
incubated
with
(N27)
neurons.
Neuronal
viability
was
assessed
using
MTT
assay.
The
effect
prooxidants,
antioxidants,
mitochondrial
Complex‐I
&
IV
activities,
BAX
expression
Spectroscopic,
Fluorometric,
RT‐PCR
methods,
respectively.
Prism‐V
software
(La
Jolla,
CA,
USA)
used
statistical
analysis.
Chemotherapeutics
dose‐dependently
inhibited
proliferation
mechanism
attributed
significant
increase
decrease
augmented
apoptosis
without
affecting
Conclusion
first
reports
reveal
induce
neurotoxicity.
Thus,
reaction
issues
substantially
persist
during
after
treatment
sometimes
never
be
completely
resolved
clinically.
Consequently,
failure
adopt
adequate
patient
care
measures
treated
certain
chemotherapeutics
might
raise
incidence
numerous
Language: Английский