T of AD with diabetes.Acknowledgments This perform was supported by the National Nature Scientific Fund of China (no. 81171196) plus the National Crucial Technologies Analysis and Development Plan from the Ministry of Science and Technology of China (no. 2012BAI10B03). CC was supported by the Australian NHMRC. Conflict of interest You will discover no actual or potential conflicts of interest.
OPENCitation: Cell Death and Disease (2013) 4, e732; doi:ten.1038/cddis.2013.257 2013 Macmillan Publishers Restricted All rights reserved 2041-4889/www.nature/cddisGlucose starvation induces cell death in K-ras-transformed cells by interfering using the hexosamine biosynthesis pathway and activating the unfolded protein responseR Palorini1,2, F Cammarata3, C Balestrieri2,six, A Monestiroli2, M Vasso1,four, C Gelfi1,four,5, L Alberghina1,two and F Chiaradonna*,1,Cancer cells, which use extra glucose than regular cells and accumulate extracellular lactate even under normoxic situations (Warburg effect), have already been reported to undergo cell death beneath glucose deprivation, whereas standard cells remain viable. Because it may be relevant to exploit the molecular mechanisms underlying this biological response to achieve new cancer therapies, in this paper we sought to recognize them by utilizing transcriptome and proteome evaluation applied to an established glucoseaddicted cellular model of transformation, namely, murine NIH-3T3 fibroblasts harboring an oncogenic K-RAS gene, compared with parental cells. Noteworthy is that the analyses performed in high- and low-glucose cultures indicate that reduction of glucose availability induces, specially in transformed cells, a significant boost inside the expression of a number of unfolded protein response (UPR) hallmark genes. We show that this response is strictly connected with transformed cell death, given that its attenuation, by decreasing protein translation or by rising cell protein folding capacity, preserves the survival of transformed cells. Such an effect can also be observed by inhibiting c-Jun NH2-terminal kinase, a pro-apoptotic signaling mediator set downstream of UPR. Strikingly, addition of N-acetyl-D-glucosamine, a certain substrate for the hexosamine biosynthesis pathway (HBP), to glucose-depleted cells fully prevents transformed cell death, stressing the crucial part of glucose in HBP fuelling to ensure UPR attenuation and increased cell survival.Ibuprofen (sodium) Interestingly, these results happen to be fully recognized in a human model of breast cancer, MDA-MB-231 cells.Fluticasone (propionate) In conclusion, we show that glucose deprivation, major to harmful accumulation of unfolded proteins in consequence of a reduction of protein glycosylation, induces a UPR-dependent cell death mechanism.PMID:24238102 These findings could open the way for new therapeutic approaches to especially kill glycolytic cancer cells. Cell Death and Illness (2013) 4, e732; doi:ten.1038/cddis.2013.257; published on the net 18 JulySubject Category: Cancer MetabolismRemodeling of power metabolism can be a recognized hallmark of cellular transformation that supports the sustained proliferation of cancer cells under conditions that restrict typical cell development.1,two Therefore, cancer cells rely largely on glycolysis for ATP production as compared with parental regular cells that use mostly oxidative phosphorylation (OXPHOS).three,four The shift of power metabolism to aerobic glycolysis is driven each by environmental development situations and by oncogenic mutations of protoncogenes and tumorsuppressor genes.5,6 Impaired mitochondrial funct.