Abstract 2304: 2-DG inhibits of N-glycosylation in glioblastoma-derived cancer stem cells

Abstract

Abstract Cancer stem cells (CSCs) are capable of unlimited self-renewal and multi-lineage differentiation. We have shown that 2-deoxy-D-glucose (2-DG), a known inhibitor of glycolysis, that is also a 2-deoxy-D-mannose can inhibits the growth of glioma-derived stem cells (GSC11) under normoxic conditions, and we hypothesize that 2-DG can affect D-glucose and D-mannose metabolism in glioblastoma derived cancer stem. Our studies showed that 2-DG affects formation of N-glycans by replacing D-mannose in glycosylation processes. We have synthesized 2-DG, D-glucose, and D-mannose labeled with deuterium at C-2 and C-6 and treated GSC11 cells with these monosaccharides to measure their effects on global N-glycan formation. Our results demonstrated that deuterium labeled 2-DG was incorporated into the N-glycans leading to the termination of the extension of oligosaccharide chain. Comparative glycomic analysis of control, 2-DG-treated, and D-mannose-rescued GSC11cells revealed a distinct modulation of the N-glycan profile. The levels of all types of N-glycans were decreased (by ∼4-fold) in 2-DG-treated GSC11 cells compared with control cells. In contrast, N-glycan synthesis in GSC11 cells could be rescued to almost “normal control” levels by adding exogenous D-mannose. D-Mannose rescue of 2-DG-treated GSC11 cells drastically reduced the incorporation of 2-DG into the N-glycans. These results indicate that 2-DG can interfere with biochemical transformations of D-mannose and that such interference might contribute to the overall antitumor effects of 2-DG. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2304. doi:10.1158/1538-7445.AM2011-2304