Sperling, Swetlana and Aung, Thiha and Martin, Sabine and Rohde, Veit and Ninkovic, Milena (2017) Riluzole: a potential therapeutic intervention in human brain tumor stem-like cells. ONCOTARGET, 8 (57). pp. 96697-96709. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
A small subpopulation of tumor stem-like cells has the capacity to initiate tumors and mediate radio- and chemoresistance in diverse cancers hence also in glioblastoma (GBM). It has been reported that this capacity of tumor initiation in the brain is mainly dependent on the body's nutrient supply. This population of so-called brain tumor initiating or brain tumor stem-like cells (BTSCs) is able to extract nutrients like glucose with a higher affinity. Riluzole, a drug approved for treating amyotrophic lateral sclerosis (ALS), was reported to possess anticancer properties, affecting the glutamate metabolism. We report that riluzole treatment inhibits the growth of brain tumor stem-like cells enriched cultures isolated from two human glioblastomas. The effects of riluzole on these cells were associated with an inhibition of a poor prognostic indicator: glucose transporter 3 (GLUT3). A decrease in GLUT3 is associated with a decrease in the p-Akt/HIF1 alpha pathway. Further, downregulation of the DNA (Cytosine-5-)-methyltransferase 1 (DNMT1) gene that causes hypermethylation of various tumor-suppressor genes and leads to a poor prognosis in GBM, was detected. Two hallmarks of cancer cells-proliferation and cell death-were positively influenced by riluzole treatment. Finally, we observed that riluzole reduced the tumor growth in in vivo CAM assay, suggesting it could be a possible synergistic drug for the treatment of glioblastoma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROSTATE-CANCER CELLS; GLUCOSE-METABOLISM; GLIOMA-CELLS; GLUT3 EXPRESSION; PATHWAY; GLIOBLASTOMA; INHIBITION; GLUTAMATE; MODULATION; GLYCOLYSIS; riluzole; human brain tumor stem-like cells; GLUT3; DNMT1; cell death |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 28 Feb 2019 07:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1849 |
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