Electronic Resource
Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells
| العنوان: | Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells |
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| المؤلفون: | Buentke, E, Nordström, Anders, Lin, H, Björklund, AC, Laane, E, Harada, M, Lu, L, Tegnebratt, T, Stone-Elander, S, Heyman, M, Söderhäll, S, Porwit, A, Östenson, CG, Shoshan, M, Tamm, K Pokrovskaja, Grandér, D |
| بيانات النشر: | Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden Macmillan Publishers Limited 2011 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs. |
| مصطلحات الفهرس: | glucocorticoids, leukemia, glycolysis, cell death, Medical Biotechnology, Medicinsk bioteknologi, Article in journal, info:eu-repo/semantics/article, text |
| DOI: | 10.1038.bcj.2011.27 |
| URL: | Blood Cancer Journal, 2044-5385, 2011, 1:e31, s. 9 |
| الاتاحة: | Open access content. Open access content info:eu-repo/semantics/restrictedAccess |
| ملاحظة: | English |
| Other Numbers: | UPE oai:DiVA.org:umu-48269 doi:10.1038/bcj.2011.27 1234183390 |
| المصدر المساهم: | UPPSALA UNIV LIBR From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1234183390 |
| قاعدة البيانات: | OAIster |
| DOI: | 10.1038.bcj.2011.27 |
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