Abstract #1127
Glutamate dehydrogenase inhibition reduces glutamine conversion into 2HG in IDH1-mutated cancer cells as detected by 13 C MRS
Tom Peeters 1 , Vincent Breukels 1 , Corina van den Heuvel 2 , Anna Navis 2 , Sanne van Lith 2 , Jack van Asten 1 , Remco Molenaar 3 , William Leenders 2 , and Arend Heerschap 1
1
Department of Radiology and Nuclear
Medicine, Radboudumc, Nijmegen, Netherlands,
2
Department
of Pathology, Radboudumc, Nijmegen, Netherlands,
3
Department
of Cell Biology and Histology, Academic Medical Center,
Amsterdam, Netherlands
Mutational changes in cytosolic isocitrate dehydrogenase
1 (IDH1) result in production of NADP
+
and
the oncometabolite D-2HG at the expense of αKG and
NADPH. Replenishment of αKG from glutamine is one of the
compensatory anaplerotic mechanisms that allow tumor
cells to survive the induced metabolic stress. We
investigated the effect of epigallocatechin gallate
(EGCG), a known inhibitor of glutamate dehydrogenase 1
(GDH1), on the fate of
13
C-glutamine
using
13
C
MRS in IDH1
wt/R132H
and
IDH1
wt/wt
cancer
cells. EGCG significantly inhibits proliferation of IDH1
wt/R132H
cells.
EGCG also prohibits the conversion of glutamine into
D-2HG and changes intracellular glutamate and glutamine
pool sizes.
How to access this content:
For one year after publication, abstracts and videos are only open to registrants of this annual meeting. Registrants should use their existing login information. Non-registrant access can be purchased via the ISMRM E-Library.
After one year, current ISMRM & ISMRT members get free access to both the abstracts and videos. Non-members and non-registrants must purchase access via the ISMRM E-Library.
After two years, the meeting proceedings (abstracts) are opened to the public and require no login information. Videos remain behind password for access by members, registrants and E-Library customers.
Click here for more information on becoming a member.
