Silencing of the human microsomal glucose-6-phosphate translocase induces glioma cell death: potential new anticancer target for curcumin |
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Authors: | Belkaid Anissa Copland Ian B Massillon Duna Annabi Borhane |
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Affiliation: | Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre BIOMED, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Que., Canada H3C 3P8. |
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Abstract: | G6P translocase (G6PT) is thought to play a crucial role in transducing intracellular signaling events in brain tumor-derived cancer cells. In this report, we investigated the contribution of G6PT to the control of U-87 brain tumor-derived glioma cell survival using small interfering RNA (siRNA)-mediated suppression of G6PT. Three siRNA constructs were generated and found to suppress up to 91% G6PT gene expression. Flow cytometry analysis of propidium iodide/annexin-V-stained cells indicated that silencing the G6PT gene induced necrosis and late apoptosis. The anticancer agent curcumin, also inhibited G6PT gene expression by more than 90% and triggered U-87 glioma cells death. Overexpression of recombinant G6PT rescued the cells from curcumin-induced cell death. Targeting G6PT expression may provide a new mechanistic rationale for the action of chemopreventive drugs and lead to the development of new anti-cancer strategies. |
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Keywords: | ATP, adenosine triphosphate CHA, chlorogenic acid 2-DG, 2-deoxy- smallcaps" >d-glucose ECM, extracellular matrix ER, endoplasmic reticulum G6P, glucose-6-phosphate G6Pase, glucose-6-phosphatase G6PT, G6P translocase GSD, glycogen storage disease MMP, matrix metalloproteinase PI, propidium iodide siRNA, small interfering ribonucleic acid |
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