Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to cause apoptosis in several types of malignant tumor cells through its interaction with the death domain-containing receptor, death receptor 5 (DR5). In the present study, we showed that co-treatment with troglitazone (TGZ), a synthetic ligand of peroxisome proliferator-activated receptor γ (PPARγ), and TRAIL synergistically induced apoptosis through DR5 upregulation in human colon cancer DLD-1 cells. TGZ elevated DR5 expression at the promoter level through the CCAAT/enhancer-binding protein homologous protein (CHOP) binding site. These results suggest that combined treatment with TGZ and TRAIL may be promising as a new therapy against malignant tumors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Apoptosis / genetics*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / pharmacology
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Binding Sites
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Cell Line, Tumor
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Chromans / pharmacology*
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Colonic Neoplasms / pathology
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Drug Synergism
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Endoplasmic Reticulum Stress / physiology
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Humans
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PPAR gamma
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Promoter Regions, Genetic
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Protein Binding
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RNA Interference
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RNA, Small Interfering
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Receptors, TNF-Related Apoptosis-Inducing Ligand / biosynthesis
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Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics*
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TNF-Related Apoptosis-Inducing Ligand / pharmacology*
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Thiazolidinediones / pharmacology*
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Transcription Factor CHOP / biosynthesis
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Transcription Factor CHOP / genetics
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Transcription Factor CHOP / metabolism*
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Troglitazone
Substances
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Antineoplastic Agents
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Apoptosis Regulatory Proteins
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Chromans
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DDIT3 protein, human
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PPAR gamma
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RNA, Small Interfering
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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TNF-Related Apoptosis-Inducing Ligand
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Thiazolidinediones
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Transcription Factor CHOP
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Troglitazone