SGLT2 inhibitor promotes mitochondrial dysfunction and ER-phagy in colorectal cancer cells
Cellular & Molecular Biology Letters,
Год журнала:
2024,
Номер
29(1)
Опубликована: Май 29, 2024
Abstract
Background
Sodium-glucose
transporter
2
(SGLT2)
inhibitors
(iSGLT2)
are
approved
medications
for
type
diabetes.
Recent
studies
indicate
that
iSGLT2
inhibit
the
growth
of
some
cancer
cells.
However,
mechanism(s)
remains
to
be
fully
elucidated.
Methods
The
SGLT2
levels
were
determined
in
normal
colon
CCD
841
CoN
and,
HCT
116,
HT-29,
SW480
and
LoVo
colorectal
(CRC)
cell
lines
by
quantitative
real-time
PCR
western
blot.
effect
canagliflozin
on
proliferation
was
examined
using
CCK-8,
as
its
role
CRC
cells
metabolism
tumorigenesis
has
been
evaluated
XF
HS
Seahorse
Bioanalyzer
flow
cytometric
analyses.
Transient
gene
silencing
experiments
analysis
protein–protein
interaction
network
conducted
evaluate
molecular
targets
Results
Data
showed
treatment
with
(50
µM)
72
h
induced
cycle
arrest
(
p
<
0.001),
impaired
glucose
energetic
promoted
apoptotic
death
ER
stress
flowing
into
autophagy
0.001)
116
HT-29
These
cellular
events
accompanied
sirtuin
3
(SIRT3)
upregulation
0.01),
also
supported
SIRT3
transient
resulting
attenuation
effects
metabolic/energetic
alterations
induction
programmed
death.
identification
validation
dipeptidyl
peptidase
4
(DPP4)
potential
common
target
assessed.
Conclusions
results
deepened
knowledge
contribution
limiting
unveiling
SGLT2/SIRT3
axis
cytotoxic
mechanisms.
Graphical
Язык: Английский
l-Carnitine and Acetyl-l-Carnitine Induce Metabolism Alteration and Mitophagy-Related Cell Death in Colorectal Cancer Cells
Nutrients,
Год журнала:
2025,
Номер
17(6), С. 1010 - 1010
Опубликована: Март 13, 2025
Background/Objectives:
Colorectal
cancer
(CRC)
remains
one
of
the
most
common
and
deadly
malignancies
worldwide,
driven
by
metabolic
reprogramming
mitochondrial
dysfunction,
which
support
tumor
growth
progression.
Several
studies
showed
that
nutrition
is
a
contributing
factor
in
prevention
management
CRC.
In
this
context,
carnitines,
amino
acid
derivatives
abundant
food
animal
origin,
such
as
meat
milk,
are
crucial
for
function.
Recently,
l-carnitine
acetyl-l-carnitine
have
received
particular
attention
due
to
their
antioxidant,
anti-inflammatory,
antitumor
properties.
However,
date,
there
no
conclusive
evidence
on
effects
CRC
or
underlying
molecular
mechanism.
Methods:
study,
we
investigated
HCT
116
HT-29
cells
homeostasis
XF
HS
Seahorse
Bioanalyzer
cell
death
pathways
flow
cytometry
western
blot
assays.
Results:
Data
reduced
viability
(p
<
0.001),
modulated
cellular
bioenergetics,
induced
oxidative
stress
0.001).
These
phenomena
promoted
autophagic
flux
mitophagy
process
via
PINK1
Parkin
modulation
after
72
h
treatment.
Of
note,
combined
treatment
with
synergistic
effect
enhanced
single
carnitines
dysfunction
0.05).
Moreover,
exposure
apoptosis,
suggesting
mechanism
involving
mitophagy-related
death.
data
were
associated
increased
SIRT4
expression
levels
0.01)
activation
AMPK
signaling
0.01).
Conclusions:
Overall,
results,
supporting
importance
nutritional
factors
management,
highlight
promising
agents
target
vulnerabilities.
Язык: Английский
Selective Modulation of PAR-2-Driven Inflammatory Pathways by Oleocanthal: Attenuation of TNF-α and Calcium Dysregulation in Colorectal Cancer Models
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 2934 - 2934
Опубликована: Март 24, 2025
Colorectal
cancer
(CRC)
remains
a
principal
contributor
to
oncological
mortality
worldwide,
with
chronic
inflammation
serving
as
fundamental
driver
of
its
pathogenesis.
Protease-activated
receptor-2
(PAR-2),
G-protein-coupled
receptor,
orchestrates
inflammation-driven
tumorigenesis
by
potentiating
NF-κB
and
Wnt/β-catenin
signaling,
thereby
fostering
epithelial-mesenchymal
transition
(EMT),
immune
evasion,
therapeutic
resistance.
Despite
pathological
significance,
targeted
modulation
PAR-2
an
underexplored
avenue
in
CRC
therapeutics.
Oleocanthal
(OC),
phenolic
constituent
extra
virgin
olive
oil,
is
recognized
for
potent
anti-inflammatory
anti-cancer
properties;
however,
regulatory
influence
on
signaling
yet
be
elucidated.
This
study
interrogates
the
impact
OC
PAR-2-mediated
inflammatory
cascades
using
HT-29
Caco-2
cell
lines
subjected
lipopolysaccharide
(LPS)-induced
activation
PAR-2.
Expression
levels
TNF-α
were
quantified
through
Western
blotting
RT-PCR,
while
ELISA
assessed
secretion.
Intracellular
calcium
flux,
pivotal
modulator
PAR-2-driven
oncogenic
inflammation,
was
evaluated
via
Fluo-4
assays.
LPS
markedly
elevated
expression
at
both
mRNA
protein
cells
(p
<
0.01,
one-way
ANOVA).
administration
(20-150
μg/mL)
elicited
dose-dependent
suppression
PAR-2,
maximal
inhibition
100-150
μg/mL
0.001,
Tukey's
post
hoc
test).
Concomitant
reductions
transcription
0.01)
secretion
0.001)
observed,
corroborating
efficacy
OC.
Additionally,
ameliorated
LPS-induced
dysregulation,
restoring
intracellular
homeostasis
concentration-dependent
manner
0.01).
Crucially,
exhibited
selectivity
leaving
PAR-1
unaltered
>
0.05),
underscoring
precision
agent.
These
findings
position
selective
CRC,
disrupting
pro-tumorigenic
microenvironment
attenuation
secretion,
pathways.
furnishes
mechanistic
insights
into
OC's
potential
nutraceutical
intervention
inflammation-associated
CRC.
Given
variability
bioavailability
content
commercial
future
investigations
should
delineate
optimal
dosing
strategies
vivo
advance
translational
therapy.
Язык: Английский
Increased colorectal cancer risk in prediabetes: A meta-analysis
World Journal of Diabetes,
Год журнала:
2025,
Номер
16(5)
Опубликована: Апрель 24, 2025
BACKGROUND
Previous
research
yielded
conflicting
results
regarding
the
association
between
prediabetes
and
colorectal
cancer
(CRC).
AIM
To
systematically
assess
incidence
of
CRC
in
individuals
with
compared
normoglycemia
via
a
meta-analysis.
METHODS
Relevant
cohort
studies
were
acquired
by
searching
MEDLINE,
Web
Science,
EMBASE.
A
random-effects
model
was
applied
to
combine
findings
after
accounting
for
heterogeneity.
Several
subgroup
analyses
conducted
impact
study
characteristics
on
results.
RESULTS
Eleven
involving
4996352
participants,
including
383917
(7.7%)
at
baseline,
analyzed
this
Over
mean
follow-up
period
6.5
years,
combined
revealed
that
baseline
had
higher
likelihood
developing
than
those
[risk
ratio
(RR)
=
1.18,
95%
confidence
interval
1.11
1.25,
P
<
0.001]
low
statistical
heterogeneity
(I
2
27%).
Subgroup
indicated
an
increased
risk
mainly
observed
defining
using
impaired
fasting
glucose
(RR
1.24)
slightly
elevated
hemoglobin
A1c
levels
1.18)
but
not
defined
tolerance
1.06).
Other
such
as
design,
country,
participant
age
sex,
duration
follow-up,
or
adjustment
body
mass
index
did
significantly
(all
>
0.05).
CONCLUSION
People
might
have
normoglycemia.
Язык: Английский