%0 Journal Article %1 Blum:2005:Cancer-Res:15705901 %A Blum, R %A Jacob-Hirsch, J %A Amariglio, N %A Rechavi, G %A Kloog, Y %D 2005 %J Cancer Res %K SHOULDREAD cancer-research fulltext glioblastoma ras %N 3 %P 999-1006 %T Ras inhibition in glioblastoma down-regulates hypoxia-inducible factor-1alpha, causing glycolysis shutdown and cell death %U https://www.ncbi.nlm.nih.gov/pubmed/15705901 %V 65 %X Active Ras and phosphatidylinositol-3-kinase-dependent pathways contribute to the malignant phenotype of glioblastoma multiformes (GBM). Here we show that the Ras inhibitor trans-farnesylthiosalicylic acid (FTS) exhibits profound antioncogenic effects in U87 GBM cells. FTS inhibited active Ras and attenuated Ras signaling to extracellular signal-regulated kinase, phosphatidylinositol-3-kinase, and Akt. Concomitantly, hypoxia-inducible factor 1alpha (HIF-1alpha) disappeared, expression of key glycolysis pathway enzymes and of other HIF-1alpha-regulated genes (including vascular endothelial growth factor and the Glut-1 glucose transporter) was down-regulated, and glycolysis was halted. This led to a dramatic reduction in ATP, resulting in a severe energy crisis. In addition, the expression of E2F-regulated genes was down-regulated in the FTS-treated cells. Consequently, U87 cell growth was arrested and the cells died. These results show that FTS is a potent down-regulator of HIF-1alpha and might therefore block invasiveness, survival, and angiogenesis in GBM.

@article{Blum:2005:Cancer-Res:15705901, abstract = {Active Ras and phosphatidylinositol-3-kinase-dependent pathways contribute to the malignant phenotype of glioblastoma multiformes (GBM). Here we show that the Ras inhibitor trans-farnesylthiosalicylic acid (FTS) exhibits profound antioncogenic effects in U87 GBM cells. FTS inhibited active Ras and attenuated Ras signaling to extracellular signal-regulated kinase, phosphatidylinositol-3-kinase, and Akt. Concomitantly, hypoxia-inducible factor 1alpha (HIF-1alpha) disappeared, expression of key glycolysis pathway enzymes and of other HIF-1alpha-regulated genes (including vascular endothelial growth factor and the Glut-1 glucose transporter) was down-regulated, and glycolysis was halted. This led to a dramatic reduction in ATP, resulting in a severe energy crisis. In addition, the expression of E2F-regulated genes was down-regulated in the FTS-treated cells. Consequently, U87 cell growth was arrested and the cells died. These results show that FTS is a potent down-regulator of HIF-1alpha and might therefore block invasiveness, survival, and angiogenesis in GBM.}, added-at = {2018-07-08T09:50:15.000+0200}, author = {Blum, R and Jacob-Hirsch, J and Amariglio, N and Rechavi, G and Kloog, Y}, biburl = {https://www.bibsonomy.org/bibtex/2bd82078acb4cad7d1b5cde50afb3c44e/marcsaric}, description = {Ras inhibition in glioblastoma down-regulates hypoxia-inducible factor-1alpha, causing glycolysis shutdown and cell death. - PubMed - NCBI}, interhash = {17db24b15e11cf8f08f51867150cc963}, intrahash = {bd82078acb4cad7d1b5cde50afb3c44e}, journal = {Cancer Res}, keywords = {SHOULDREAD cancer-research fulltext glioblastoma ras}, month = feb, number = 3, pages = {999-1006}, pmid = {15705901}, timestamp = {2018-07-08T09:50:38.000+0200}, title = {Ras inhibition in glioblastoma down-regulates hypoxia-inducible factor-1alpha, causing glycolysis shutdown and cell death}, url = {https://www.ncbi.nlm.nih.gov/pubmed/15705901}, volume = 65, year = 2005 }