Soloxolone para-methylanilide effectively suppresses aggressive phenotype of glioblastoma cells including TGF-β1-induced glial-mesenchymal transition in vitro and inhibits growth of U87 glioblastoma xenografts in mice
Kirill V. Odarenko,
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Aleksandra V. Sen’kova,
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Oksana V. Salomatina
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et al.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: July 29, 2024
Soloxolone
amides
are
semisynthetic
triterpenoids
that
can
cross
the
blood-brain
barrier
and
inhibit
glioblastoma
growth
both
in
vitro
vivo
.
Here
we
investigate
impact
of
these
compounds
on
processes
associated
with
invasiveness
therapy
resistance.
Screening
soloxolone
against
cells
revealed
ability
compound
7
(soloxolone
para
-methylanilide)
to
transforming
factor-beta
1
(TGF-β1)-induced
glial-mesenchymal
transition
Compound
inhibited
morphological
changes,
wound
healing,
transwell
migration,
expression
mesenchymal
markers
(N-cadherin,
fibronectin,
Slug)
TGF-β1-induced
U87
U118
cells,
while
restoring
their
adhesiveness.
Confocal
microscopy
molecular
docking
showed
reduced
SMAD2/3
nuclear
translocation
probably
by
direct
interaction
TGF-β
type
I
II
receptors
(TβRI/II).
In
addition,
suppressed
stemness
as
evidenced
inhibition
colony
forming
ability,
spheroid
growth,
aldehyde
dehydrogenase
(ALDH)
activity.
Furthermore,
exhibited
a
synergistic
effect
temozolomide
(TMZ)
cell
viability.
Using
N-acetyl-L-cysteine
(NAC)
flow
cytometry
analysis
Annexin
V-FITC-,
propidium
iodide-,
DCFDA-stained
was
found
synergize
cytotoxicity
TMZ
inducing
ROS-dependent
apoptosis.
Further
studies
,
alone
or
combination
TMZ,
effectively
xenograft
tumors
mice.
Thus,
demonstrated
promising
potential
component
for
glioblastoma,
reducing
its
increasing
sensitivity
chemotherapy.
Language: Английский
Oceanic Breakthroughs: Marine-Derived Innovations in Vaccination, Therapy, and Immune Health
Chiara Gamberi,
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Chad L. Leverette,
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Aubrey K. Davis
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et al.
Vaccines,
Journal Year:
2024,
Volume and Issue:
12(11), P. 1263 - 1263
Published: Nov. 8, 2024
The
vast,
untapped
potential
of
the
world's
oceans
is
revealing
groundbreaking
advancements
in
human
health
and
vaccination.
Microalgae
such
as
Language: Английский