Meeting Banner
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.

This abstract and the presentation materials are available to members only; a login is required.

Join Here