Preclinical pharmaco-toxicological screening of biomimetic melanin-like nanoparticles as a potential therapeutic strategy for cutaneous melanoma
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Фев. 6, 2025
Despite
its
rarity,
cutaneous
melanoma
(CM)
represents
the
deadliest
skin
cancer
with
a
high
mortality
rate,
an
incidence
on
rise,
and
limited
therapeutic
options
at
present.
Melanin
is
polymeric
pigment
naturally
produced
within
melanocytes
CM
cells
that
gained
noteworthy
attention
due
to
pharmacological
properties,
potential
for
design
of
nanoplatforms
biomedical
applications.
Up
date,
utilization
melanin-like
nanoparticles
(MEL-NPs)
in
treatment
has
been
well-documented,
although
their
efficacy
therapy
remains
scarcely
investigated.
The
current
study
presents
preclinical
evaluation
MEL-NPs
as
nanomedicine
management.
were
through
oxidative
polymerization
dopamine
characterized
via
electron
microscopy
UV-VIS
spectroscopy.
antioxidant
activity
was
determined
by
using
DPPH
method.
cytotoxic,
anti-migratory,
anti-clonogenic,
pro-oxidant
pro-apoptotic
properties
investigated
vitro
applying
MTT
viability
test,
bright-field
immunofluorescence
microscopy,
DCFDA/H2DCFDA
scratch
assay,
colony
formation
RT-qPCR.
irritant
anti-angiogenic
effects
assessed
ovo
vascularized
chorioallantoic
membrane
(CAM).
as-made
presented
spherical
morphology,
average
size
85.61
nm,
broad
absorption
spectrum,
strong
activity.
After
24
h
treatment,
exerted
selective
cytotoxicity
SH-4
B164A5
compared
HEMa,
HaCaT,
JB6
Cl
41-5a
healthy
cells,
except
concentration
100
µg/mL,
which
declined
under
70%.
Additionally,
accumulated
intracellular
space
forming
perinuclear
coating,
inhibited
motility
clonogenic
potential,
increased
stress,
targeted
epithelial-to-mesenchymal
transition,
induced
apoptosis
altering
cell
nuclear
aspect,
F-actin
tubulin
distribution,
modulating
expression
pro-
anti-apoptotic
markers.
In
ovo,
lacked
vascular
toxic
effects,
while
exerting
angio-suppressive
demonstrated
promising
anti-melanoma
showing
cytotoxicity,
anti-invasive
effect
inhibiting
CAM
angiogenesis,
these
novel
findings
contributing
future
research
application
this
nanoplatform
therapy.
Язык: Английский
Unveiling the Pharmacological Mechanism of Cosmos caudatus Compounds as Lung Cancer Drug Candidates: Pharmacology Networking, Molecular Docking, and Experimental Validation
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 3, 2025
Abstract
Cosmos
caudatus
is
a
traditional
Indonesian
medicinal
plant
commonly
used
in
the
treatment
of
cancer,
hypertension,
diabetes,
osteoporosis,
and
other
potential
health
conditions.
However,
mechanisms
behind
its
compounds,
targets,
diseases,
disease
pathways,
their
molecular
profiles
treating
lung
cancer
remain
unclear.
Therefore,
comprehensive
approach
required
to
study
these
by
integrating
metabolomics,
bioinformatics,
vitro
experimental
validation
explore
active
involved
cancer.
The
metabolomic
identified
66
compounds
leaves,
which
13
met
criteria
for
gastrointestinal
drugs.
3',4',5,7-tetrahydroxyflavone,
AKT1
target,
neoplasms
PIP3
activating
AKT
signalling
pathway,
each
became
core
target
with
highest
degree
value
pharmacological
network
formed.
In
protein-protein
interaction
(PPI)
network,
again
value.
Gene
Ontology
(GO)
functional
enrichment
analysis
revealed
that
biological
processes,
functions,
cellular
components,
KEGG
pathways
were
phosphorylation,
cytoplasm,
protein
binding,
respectively.
three
best
binding
energy
hydrogen
bonding
3',4',5,7-tetrahydroxyflavone-AKT1
(9C1W),
gamma-mangostin-EGFR
(3P0V),
cratoxyarborenone
E-TNF
(1XU1),
energies
-10.8,
-8.9,
−
9.6
kcal/mol,
methanol
extracts
inhibited
A549
cells
at
concentration
156.12
µg/mL.
combination
methods
provides
insights
into
C.
Язык: Английский
Unveiling the Pharmacological Mechanism of Cosmos Caudatus Compounds as Lung Cancer Drug Candidates: Pharmacology Networking, Molecular Docking, and Experimental Validation
Journal of Pharmaceutical Innovation,
Год журнала:
2025,
Номер
20(3)
Опубликована: Апрель 21, 2025
Язык: Английский
Widely metabolomic combined with transcriptome analysis to build a bioactive compound regulatory network for the fruit growth cycle in Pseudocydonia sinensis
Food Chemistry,
Год журнала:
2024,
Номер
456, С. 139933 - 139933
Опубликована: Май 31, 2024
Язык: Английский
Aspirin–Fisetin Combinatorial Treatment Exerts Cytotoxic and Anti-Migratory Activities in A375 Malignant Melanoma Cells
Medicina,
Год журнала:
2024,
Номер
60(7), С. 1125 - 1125
Опубликована: Июль 12, 2024
Background
and
Objectives:
Malignant
melanoma
(MM)
remains
one
of
the
most
aggressive
cancers
worldwide,
presenting
a
limited
number
therapeutic
options
at
present.
Aspirin
(ASA),
broadly
used
non-steroid
anti-inflammatory
medicine,
has
recently
emerged
as
candidate
for
repurposing
in
cancer
management,
due
to
its
potential
treatment
several
neoplasms
which
include
MM.
Fisetin
(FIS)
is
flavonoid
phytoestrogen
instilled
with
multispectral
pharmacological
activities,
including
potent
anti-melanoma
property.
The
present
study
aimed
assess
improved
anti-neoplastic
effect
resulting
from
association
ASA
FIS
MM
therapy.
Materials
Methods:
was
conducted
using
A375
cell
line
an
experimental
model
Cell
viability
assessed
via
MTT
test.
morphology
confluence
were
evaluated
bright-field
microscopy.
aspect
nuclei
tubulin
fibers
observed
through
immunofluorescence
staining.
irritant
anti-angiogenic
determined
on
chorioallantoic
membrane
chicken
fertilized
eggs.
Results:
main
findings
related
herein
demonstrated
that
2.5
mM
+
(5,
10,
15,
20
µM)
combination
exerted
higher
cytotoxicity
cells
compared
individual
compounds,
outlined
by
concentration-dependent
massive
reduction
viability,
loss
confluence,
shrinkage
rounding,
apoptotic-like
nuclear
features,
constriction
disruption
filaments,
increased
apoptotic
index,
suppressed
migratory
ability.
µM
lacked
inhibited
blood-vessel
formation
ovo.
Conclusion:
These
results
stand
first
contributions
combinatorial
treatment.
Язык: Английский
Paraptosis—A Distinct Pathway to Cell Death
C Kunst,
Deniz Tümen,
Martha Ernst
и другие.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(21), С. 11478 - 11478
Опубликована: Окт. 25, 2024
Cell
death
is
a
critical
biological
process
necessary
for
development,
tissue
maintenance,
and
defense
against
diseases.
To
date,
more
than
20
forms
of
cell
have
been
identified,
each
defined
by
unique
molecular
pathways.
Understanding
these
different
essential
investigating
the
pathogenesis
diseases
such
as
cancer,
neurodegenerative
disorders,
autoimmune
conditions
developing
appropriate
therapies.
Paraptosis
distinct
form
regulated
characterized
cytoplasmic
vacuolation
dilatation
cellular
organelles
like
mitochondria
endoplasmic
reticulum
(ER).
It
several
signaling
pathways,
instance,
those
associated
with
ER
stress,
calcium
overload,
oxidative
specific
cascades
insulin-like
growth
factor
I
receptor
(IGF-IR)
its
downstream
pathways
comprising
mitogen-activated
protein
kinases
(MAPKs)
Jun
N-terminal
kinase
(JNK).
has
observed
in
diverse
contexts,
including
development
stress
responses
neuronal,
retinal,
endothelial,
muscle
cells.
The
induction
paraptosis
increasingly
important
anticancer
therapy,
it
targets
non-apoptotic
tumor
cells,
which
can
be
utilized
to
induce
death.
This
approach
enhances
treatment
efficacy
addresses
drug
resistance,
particularly
cases
where
cancer
cells
are
resistant
apoptosis.
Combining
paraptosis-inducing
agents
traditional
therapies
holds
promise
enhancing
overcoming
suggesting
valuable
strategy
therapy.
Язык: Английский
Quercetin Enhances 5-Fluorouracil-Driven Cytotoxicity Dose-Dependently in A375 Human Melanoma Cells
Andrea Roman,
Andreea Smeu,
Ana Lascu
и другие.
Life,
Год журнала:
2024,
Номер
14(12), С. 1685 - 1685
Опубликована: Дек. 19, 2024
Cutaneous
melanoma
(CM)
represents
a
severe
skin
cancer
with
rising
incidence
at
present
and
limited
treatment
options.
5-Fluorouracil
(5-FU)
is
widely
used,
including
for
CM;
however,
the
innate
resistance
of
this
to
conventional
therapy
remains
problematic.
Quercetin
(QUE)
flavonoid
that
can
sensitize
cells
antitumor
agents
such
as
5-FU.
However,
potential
sensitization
capability
CM
5-FU
has
scarcely
been
determined,
investigated
herein.
Therefore,
A375
were
tested
in
terms
their
cell
viability,
confluence,
morphological
changes.
Their
nuclear
cytoskeletal
aspects,
clonogenic
potential,
ovo
properties
also
followed.
The
results
showed
50%
inhibitory
concentrations
(IC50s)
QUE
determined
by
proliferation
assay
11.56
11.08
µM,
respectively.
addition
(10
µM)
(5–50
increased
cytotoxic
potential.
A
significant
decline
viability
(up
43.51%),
loss
chromatin
condensation
dysmorphology,
tubulin
F-actin
constriction,
suppressed
ability
noted.
+
association
was
non-irritating
chorioallantoic
membrane
an
antiangiogenic
effect
ovo.
Thus,
our
highlight
combining
enhance
safe
profile
Язык: Английский