British Journal of Pharmacology,
Год журнала:
2023,
Номер
180(23), С. 2937 - 2955
Опубликована: Сен. 23, 2023
Sunitinib
is
the
first-line
drug
for
renal
cell
carcinoma
(RCC)
treatment.
However,
patients
who
received
sunitinib
treatment
will
ultimately
develop
resistance
after
6-15
months,
creating
a
huge
obstacle
to
current
of
carcinoma.
Therefore,
it
urgent
clarify
mechanisms
and
new
strategies
overcome
it.
In
this
review,
in
have
been
summarized
based
on
five
topics:
activation
bypass
or
alternative
pathway,
inadequate
accumulation,
tumour
microenvironment,
metabolic
reprogramming
epigenetic
regulation.
Furthermore,
present
potential
biomarkers,
as
well
overcoming
carcinoma,
are
also
covered.
Journal of Medicinal Chemistry,
Год журнала:
2023,
Номер
66(20), С. 14357 - 14376
Опубликована: Окт. 5, 2023
Inhibitors
of
histone
deacetylases
(HDACs)
have
received
special
attention
as
novel
anticancer
agents.
Among
various
types
synthetic
inhibitors,
benzamides
constitute
an
important
class,
and
one
is
approved
drug
(chidamide).
Here,
we
present
a
class
HDAC
inhibitors
containing
the
N-(2-aminophenyl)-benzamide
functionality
zinc-binding
group
linked
to
cap
groups,
including
amino
acids
pyroglutamic
acid
proline.
We
identified
that
inhibit
HADC1
HDAC2
at
nanomolar
concentrations,
with
antiproliferative
activity
micromolar
concentrations
against
A549
SF268
cancer
cell
lines.
Docking
studies
shed
light
on
mode
binding
benzamide
HDAC1,
whereas
cellular
analysis
revealed
downregulated
expression
EGFR
mRNA
protein.
Two
were
investigated
in
mouse
model
bleomycin-induced
pulmonary
fibrosis,
both
showed
efficacy
preventative
dosing
schedule.
N-(2-Aminophenyl)-benzamide
I
HDACs
might
lead
new
approaches
for
treating
fibrotic
disorders.
Molecular Medicine Reports,
Год журнала:
2023,
Номер
28(4)
Опубликована: Сен. 6, 2023
In
recent
years,
inhibiting
tumor
cell
activity
by
triggering
ferroptosis
has
become
a
research
hotspot.
The
development
of
generic
targeted
nanotherapeutics
might
bring
new
ideas
for
non‑invasive
applications.
Currently,
the
potential
mechanism
underlying
universal
application
paclitaxel
(PTX)‑loaded
iron
oxide
nanoparticles
(IONP@PTX)
to
different
types
tumors
is
unclear.
present
study
aimed
prepare
IONP@PTX
cancer
therapy
and
further
explore
mechanisms
inhibitory
effects
this
material
on
NCI‑H446
human
small
lung
brain
M059K
malignant
glioblastoma
lines.
First,
CCK‑8
assay
was
performed
determine
viability,
then
combination
index
evaluating
drug
interaction
effect
evaluated.
Intracellular
reactive
oxygen
species
(ROS)
lipid
peroxidation
levels
were
monitored
using
DCFH‑DA
fluorescent
probe
C11‑BODIPY™
probe,
respectively.
Furthermore,
western
blotting
expression
autophagy‑
death‑related
proteins.
experimental
results
showed
that,
compared
with
either
IONP
monotherapy,
PTX
or
+
PTX,
exerted
synergistic
viability
both
types,
significantly
increased
total
ion
concentration,
ROS
levels.
autophagy‑related
proteins
Beclin
1
histone
deacetylase
6
(HDAC6)
in
lines
(P<0.05),
light
chain
3
(LC3)‑II/I
cells
(P<0.05)
decreased
that
sequestosome1
(p62)
(P<0.05).
Moreover,
addition
rapamycin
enhanced
IONP@PTX‑induced
upregulation
1,
LC3‑II/I
HDAC6
downregulation
mTORC1
protein
p62
suggesting
induces
ferroptosis,
most
likely
through
autophagy.
Collectively,
findings
show
works
synergistically
induce
via
autophagic
pathway.
British Journal of Pharmacology,
Год журнала:
2023,
Номер
180(23), С. 2937 - 2955
Опубликована: Сен. 23, 2023
Sunitinib
is
the
first-line
drug
for
renal
cell
carcinoma
(RCC)
treatment.
However,
patients
who
received
sunitinib
treatment
will
ultimately
develop
resistance
after
6-15
months,
creating
a
huge
obstacle
to
current
of
carcinoma.
Therefore,
it
urgent
clarify
mechanisms
and
new
strategies
overcome
it.
In
this
review,
in
have
been
summarized
based
on
five
topics:
activation
bypass
or
alternative
pathway,
inadequate
accumulation,
tumour
microenvironment,
metabolic
reprogramming
epigenetic
regulation.
Furthermore,
present
potential
biomarkers,
as
well
overcoming
carcinoma,
are
also
covered.
