biostudies-literatureSieber-Frank JHector StiftungElse Kröner-Fresenius-Stiftung6807-6822https://www.ebi.ac.uk/biostudies/studies/S-EPMC8495295biostudies-literatureUnknown10(19)Rocaglates are natural compounds that have been extensively studied for their ability to inhibit translation initiation. Rocaglates represent promising drug candidates for tumor treatment due to their growth-inhibitory effects on neoplastic cells. In contrast to natural rocaglates, synthetic analogues of rocaglates have been less comprehensively characterized, but were also shown to have similar effects on the process of protein translation. Here, we demonstrate an enhanced growth-inhibitory effect of synthetic rocaglates when combined with glucose anti-metabolite 2-deoxy-D-glucose (2DG) in different cancer cell lines. Moreover, we unravel a new aspect in the mechanism of action of synthetic rocaglates involving reduction of glucose uptake mediated by downregulation or abrogation of glucosCancer medicineTreatment resistance analysis reveals GLUT-1-mediated glucose uptake as a major target of synthetic rocaglates in cancer cells.PMC84952952016_A61M84Kohler RPrigge ESKopitz JHenkel TKrammer PHvon Knebel Doeberitz MSchubert TFischl WKloor MAndresen CKalteis SSieber-Frank JStark HJCasari GLi-Weber MAhadova AfalseTreatment resistance analysis reveals GLUT-1-mediated glucose uptake as a major target of synthetic rocaglates in cancer cells.Rocaglates are natural compounds that have been extensively studied for their ability to inhibit translation initiation. Rocaglates represent promising drug candidates for tumor treatment due to their growth-inhibitory effects on neoplastic cells. In contrast to natural rocaglates, synthetic analogues of rocaglates have been less comprehensively characterized, but were also shown to have similar effects on the process of protein translation. Here, we demonstrate an enhanced growth-inhibitory effect of synthetic rocaglates when combined with glucose anti-metabolite 2-deoxy-D-glucose (2DG) in different cancer cell lines. Moreover, we unravel a new aspect in the mechanism of action of synthetic rocaglates involving reduction of glucose uptake mediated by downregulation or abrogation of glucos2021-01-01T00:00:00Z2021 Oct2026-05-08T20:46:48.184Z2022-02-11T12:00:37.558ZS-EPMC84952953454600010.1002/cam4.4212