2-Deoxy-d-glucose increases GFAT1 phosphorylation resulting in endoplasmic reticulum-related apoptosis via disruption of protein N-glycosylation in pancreatic cancer cells.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study in cancer cell lines without human or animal subjects
PubMed 29753740 · doi:10.1016/j.bbrc.2018.05.041
What was done
Conducted proteomic analysis and molecular assays on pancreatic cancer cell lines treated with 2-deoxy-d-glucose (2DG). Measured differential protein expression, glutamine:fructose 6-phosphate aminotransferase 1 (GFAT1) mRNA and protein levels, total N-glycoproteins, GFAT1 phosphorylation by AMPK, and endoplasmic reticulum (ER) stress markers (GRP78, CHOP). Also evaluated the combination of 2DG and metformin on AMPK activation, protein N-glycosylation, and cell growth.
What was found
Proteomic analysis revealed 80 differentially expressed proteins after 2DG treatment, with upregulation of GFAT1 and phosphohexose metabolism proteins. Despite GFAT1 upregulation, 2DG led to decreased total N-glycoproteins alongside AMPK-mediated GFAT1 phosphorylation. 2DG elevated ER stress markers GRP78 and CHOP. Metformin additively activated AMPK, synergistically enhancing the reduction of protein N-glycosylation and cell growth inhibition. No exact numerical values or effect sizes were reported in the abstract.
Why it matters
Demonstrates that 2DG induces ER-stress-mediated pancreatic cancer cell growth inhibition through AMPK-dependent GFAT1 phosphorylation and N-glycosylation disruption, an effect amplified by metformin.
Limits
In vitro cell line study only, lacking in vivo animal models or human data. The abstract omits specific cell line identities, replicate numbers, drug doses, and quantitative effect sizes.
Cited by
- supports 2-deoxyglucose increases protein chaperones, including glucose-regulated protein 78 (GRP78).