Melatonin,
the
hormone
of
pineal
gland,
possesses
a
range
physiological
functions,
and
recently,
its
anticancer
effect
has
become
more
apparent.
A
thorough
understanding
molecular
alterations
in
components
several
signaling
pathways
as
new
targets
for
cancer
therapy
is
needed
because
current
innate
restrictions
such
drug
toxicity,
side
effects,
acquired
or
de
novo
resistance.
The
PI3K/Akt/mTOR
pathway
overactivated
many
solid
tumors,
breast
ovarian
cancers.
This
normal
cells
essential
growth,
proliferation,
survival.
However,
it
an
undesirable
characteristic
malignant
cells.
We
have
reviewed
multiple
studies
about
melatonin
on
cancer,
focusing
pathway.
Melatonin
exerts
inhibitory
effects
via
mechanisms.
A:
Downregulation
downstream
upstream
phosphatase
tensin
homolog
(PTEN),
phosphatidylinositol
(3,4,5)-trisphosphate
kinase
(PI3K),
p-PI3K,
Akt,
p-Akt,
mammalian
target
rapamycin
(mTOR),
mTOR
complex1
(mTORC1).
B:
Apoptosis
induction
by
decreasing
MDM2
expression,
mTOR,
which
leads
to
Bad
activation
addition
Bcl-XL
p53
inhibition.
C:
Induction
autophagy
activating
ULK1
after
inhibition,
resulting
Beclin-1
phosphorylation.
with
AMBRA1
VPS34
promotes
PI3K
complex
I
activity
overlaps
other
intracellular
AMP-activated
protein
(AMPK),
Wnt/β-catenin,
mitogen-activated
(MAPK),
similar
pathways.
Cancer
can
benefit
from
how
these
interact
affects
Journal of Pineal Research,
Год журнала:
2022,
Номер
73(3)
Опубликована: Авг. 20, 2022
The
oncostatic
effects
of
melatonin
correlate
with
increased
reactive
oxygen
species
(ROS)
levels,
but
how
induces
this
ROS
generation
is
unknown.
In
the
present
study,
we
aimed
to
elucidate
two
seemingly
opposing
actions
regarding
its
relationship
free
radicals.
We
analyzed
on
head
and
neck
squamous
cell
carcinoma
lines
(Cal-27
SCC-9),
which
were
treated
0.5
or
1
mM
melatonin.
further
examined
potential
induce
apoptosis
in
Cal-27
xenograft
mice.
Here
report
that
mediates
cancer
by
driving
mitochondrial
reverse
electron
transport
(RET)
production.
Melatonin-induced
changes
tumoral
metabolism
led
activity,
which,
turn,
induced
ROS-dependent
uncoupling.
Interestingly,
complex
inhibitors,
including
rotenone,
abolished
elevation
indicating
via
RET.
Melatonin
also
membrane
CoQ10
H2
/CoQ10
ratio
elevate
production,
are
essential
conditions
for
found
genetic
manipulation
cells
alternative
oxidase,
transfers
electrons
from
QH2
oxygen,
inhibited
melatonin-induced
generation,
apoptosis.
RET
restored
effect,
highlighting
importance
as
site
These
results
illustrate
production
crucial
factors
melatonin's
establish
dual
effect
protecting
normal
inducing
cells.
Cellular & Molecular Biology Letters,
Год журнала:
2023,
Номер
28(1)
Опубликована: Май 2, 2023
Oral
squamous
cell
carcinomas
are
one
of
the
most
common
cancers
worldwide
with
aggressive
behavior
and
poor
prognosis.
Reactive
oxygen
species
(ROS)
associated
cancer
cause
various
types
regulated
death
(RCD).
Inducing
RCD
pathway
by
modulating
ROS
levels
is
imperative
to
conquer
cancers.
The
aim
this
study
investigate
synergistic
anticancer
effects
melatonin
erastin
on
modulation
subsequent
induction.Human
tongue
carcinoma
lines
(SCC-15
cells)
were
treated
melatonin,
erastin,
or
their
combination.
Cell
viability,
levels,
autophagy,
apoptosis,
ferroptosis
tested
according
results
PCR
array,
which
verified
with/without
induction
inhibition
H2O2
N-acetyl-L-cysteine,
respectively.
In
addition,
a
mouse-based
subcutaneous
oral
xenograft
model
was
constructed
identify
combination
in
isolated
tumor
tissues.ROS
increased
administration
at
high
concentrations
(mM),
enhanced
malonic
dialdehyde,
ROS,
lipid
reduced
glutamate
glutathione.
SQSTM1/p62,
LC3A/B,
cleaved
caspase-3,
PARP1
protein
SCC-15
cells
also
plus
treatment,
further
as
accumulated,
decreased
suppressed.
Combined
treatment
markedly
size
vivo,
demonstrated
no
obvious
systemic
side
effects,
significantly
apoptosis
tissues,
parallel
autophagy
levels.Melatonin
combined
exhibits
without
adverse
reactions.
Herein,
might
become
promising
alternative
strategy
for
treatment.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Март 11, 2024
Apoptosis
is
a
programmed
cell
death
comprising
two
signaling
cascades
including
the
intrinsic
and
extrinsic
pathways.
This
process
has
been
shown
to
be
involved
in
therapy
response
of
different
cancer
types,
making
it
an
effective
target
for
treating
cancer.
Cancer
considered
challenging
issue
global
health.
cells
possess
six
biological
characteristics
during
their
developmental
known
as
hallmarks.
Hallmarks
include
continuous
growth
signals,
unlimited
proliferation,
resistance
proliferation
inhibitors,
apoptosis
escaping,
active
angiogenesis,
metastasis.
Sesquiterpene
lactones
are
one
large
diverse
groups
planet-derived
phytochemicals
that
can
used
sources
variety
drugs.
Some
sesquiterpene
many
activities
such
anti-inflammatory,
anti-viral,
anti-microbial,
anti-malarial,
anticancer,
anti-diabetic,
analgesic.
review
article
briefly
overviews
pathways
interactions
between
modulators
both
Also,
present
summarizes
potential
effects
on
lines
animal
models.
The
main
purpose
give
clear
picture
current
knowledge
about
pro-apoptotic
various
cancers
provide
future
direction
therapeutics.
Journal of Pineal Research,
Год журнала:
2021,
Номер
71(3)
Опубликована: Июль 21, 2021
Melatonin,
an
endogenous
hormone,
plays
protective
roles
in
cancer.
In
addition
to
regulating
circadian
rhythms,
sleep,
and
neuroendocrine
activity,
melatonin
functions
various
survival
pathways.
However,
the
mechanisms
of
regulation
cancer
remain
unknown.
present
study,
we
performed
a
comprehensive
characterization
regulators
9125
tumor
samples
across
33
types
using
multi-omic
data
from
The
Cancer
Genome
Atlas
Cell
Line
Encyclopedia.
genomic
landscape,
identified
heterozygous
amplification
AANAT
GPR50,
deletion
PER3,
CYP2C19,
MTNR1A
as
dominant
alteration
events.
Expression
analysis
revealed
methylation-mediated
downregulation
melatonergic
regulator
expression.
addition,
found
that
expression
could
be
used
predict
patient
cancers.
depth,
microRNA
(miRNA)
miRNA-mRNA
interaction
network,
deregulated
miRNAs
were
involved
secretion
metabolism
by
targeting
clock
genes.
Pathway
showed
associated
with
inhibition
apoptosis,
cell
cycle,
DNA
damage
response,
activation
RAS/MAPK
RTK
signaling
Importantly,
mining
Genomics
Drug
Sensitivity
database,
discovered
number
potential
drugs
might
target
regulators.
summary,
this
study
clinical
characteristics
cancers,
which
clarify
relationship
between
tumorigenesis.
Our
findings
also
provide
novel
approach
for
treatment
Obesity
is
a
chronic
condition
whose
management
critical
challenge
for
physicians.
The
scientific
community
has
increased
its
focus
on
the
molecular
mechanisms
involved
in
obesity
etiopathogenesis
to
better
manage
patients
with
and
associated
complications.
tight
connection
between
adipose
tissue
immune
system
been
demonstrated
play
crucial
role
inflammation,
melatonin
important
circadian
rhythm
regulation
metabolic
homeostasis,
which
it
orchestrates
several
inflammation.
Melatonin
also
regulates
innate
adaptive
immunity;
antioxidant
properties
are
linked
reduced
predisposition
infection
weight
gain
through
modulation
of
response,
significant
beneficial
effect
inflammation
and,
consequently,
state.
Low
levels
have
obesity,
supplementation
can
reduce
body
weight,
improve
profile,
ameliorate
responses
pro-inflammatory
stimuli.
mainly
related
improved
oxidative
stress
signaling,
adipokine
secretion,
switching
from
white-to-brown
phenotype
activity.
Moreover,
by
controlling
recently
emerged
as
pivotal
mechanism
lipid
glucose
metabolism
dysfunction
adipose,
muscle,
liver
tissues.
may
regulate
acting
directly
thymus
morphology
activity
well
modulating
inflammatory
states
during
infections.
association
response
coordinated
Toll-like
receptors,
rhythmically
expressed
day.
Their
expression
be
strongly
modulated
their
signaling
highly
inhibited
melatonin.
current
review
summarizes
studies
melatonin-induced
regulation,
particularly
obesity-associated
systemic
