Induction of apoptosis in glioma cell lines by TRAIL/Apo-2l.
TRAIL/Apo-2L, a novel cytokine, is a member of the tumor necrosis factor (TNF) family and serves as an extracellular signal triggering apoptosis. TRAIL/Apo-2L is capable of killing various transformed cells but not unstimulated primary T cells. In this study, five human glioma cells (U87, U118, U178, U563, and A172) were examined for their susceptibility to the apoptotic effects of TRAIL/Apo-2L. TRAIL/Apo-2L cDNA was isolated by RT-PCR, and recombinant TRAIL/Apo-2L protein was purified by the pMAL-c2 system (New England Biolabs, Beverly, MA). Exposure of A172 cells to bacterially expressed soluble TRAIL/Apo-2L fusion protein at a concentration of 1 microg/ml resulted in significant cell death over a 24-h period. Three experiments were performed to suggest that the TRAIL/Apo-2L killing was through the induction of apoptosis of A172 target cells. In addition, the expression of TRAIL/Apo-2L in different glioma cells was found to be variable, and TRAIL/Apo-2L-induced apoptosis was in a cell type-dependent manner. Some correlation between the susceptibility to TRAIL/Apo-2L and the expression level of one of its cognate receptors, DR4, was observed. In addition, cycloheximide worked synergistically with TRAIL/Apo-2L to induce apoptosis in glioma cells.
Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, HeFei, China. wumian88@yahoo.com
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Das
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Zhu
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Wong
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha