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Acetate supplementation induces growth arrest of NG2/PDGFRα-positive oligodendroglioma-derived tumor-initiating cells.
[canavan disease]
Cancer
is
associated
with
globally
hypoacetylated
chromatin
and
considerable
attention
has
recently
been
focused
on
epigenetic
therapies
.
N-
acetyl-
L-
aspartate
(
NAA
)
,
the
primary
storage
form
of
acetate
in
the
brain
,
and
aspartoacylase
(
ASPA
)
,
the
enzyme
responsible
for
NAA
catalysis
to
generate
acetate
and
ultimately
acetyl-
Coenzyme
A
for
histone
acetylation
,
are
reduced
in
oligodendroglioma
.
The
short
chain
triglyceride
glyceryl
triacetate
(
GTA
)
,
which
increases
histone
acetylation
and
inhibits
histone
deacetylase
expression
,
has
been
safely
used
for
acetate
supplementation
in
Canavan
disease
,
a
leukodystrophy
due
to
ASPA
mutation
.
We
demonstrate
that
GTA
induces
cytostatic
G
0
growth
arrest
of
oligodendroglioma
-derived
cells
in
vitro
,
without
affecting
normal
cells
.
Sodium
acetate
,
at
doses
comparable
to
that
generated
by
complete
GTA
catalysis
,
but
not
glycerol
also
promoted
growth
arrest
,
whereas
long
chain
triglycerides
promoted
cell
growth
.
To
begin
to
elucidate
its
mechanism
of
action
,
the
effects
of
GTA
on
ASPA
and
acetyl-
CoA
synthetase
protein
levels
and
differentiation
of
established
human
oligodendroglioma
cells
(
HOG
and
Hs
683
)
and
primary
tumor
-derived
oligodendroglioma
cells
that
exhibit
some
features
of
cancer
stem
cells
(
grade
II
OG
33
and
grade
III
OG
35
)
relative
to
an
oligodendrocyte
progenitor
line
(
Oli
-
Neu
)
were
examined
.
The
nuclear
localization
of
ASPA
and
acetyl-
CoA
synthetase-
1
in
untreated
cells
was
regulated
during
the
cell
cycle
.
GTA-mediated
growth
arrest
was
not
associated
with
apoptosis
or
differentiation
,
but
increased
expression
of
acetylated
proteins
.
Thus
,
GTA-mediated
acetate
supplementation
may
provide
a
safe
,
novel
epigenetic
therapy
to
reduce
the
growth
of
oligodendroglioma
cells
without
affecting
normal
neural
stem
or
oligodendrocyte
progenitor
cell
proliferation
or
differentiation
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated