Abstract
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various malignant cells, several cancers including human hepatocellular carcinoma (HCC) exhibit potent resistance to TRAIL-induced cell death. The aim of this study is to evaluate the anti-cancer potential of capsaicin in TRAIL-induced cancer cell death. As indicated by assays that measure phosphatidylserine exposure, mitochondrial activity and activation of caspases, capsaicin potentiated TRAIL-resistant cells to lead to cell death. In addition, we found that capsaicin induces the cell surface expression of TRAIL receptor DR5, but not DR4 through the activation Sp1 on its promoter region. Furthermore, we investigated that capsaicin-induced DR5 expression and apoptosis are inhibited by calcium chelator or inhibitors for calmodulin-dependent protein kinase. Taken together, our data suggest that capsaicin sensitizes TRAIL-mediated HCC cell apoptosis by DR5 up-regulation via calcium influx-dependent Sp1 activation.
Copyright © 2011 Elsevier Inc. All rights reserved.
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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Blotting, Western
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Calcium / metabolism*
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Capsaicin / pharmacology*
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cell Culture Techniques
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Cell Line, Tumor
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Cell Survival / drug effects
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Chromatin Immunoprecipitation
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Drug Resistance, Neoplasm / drug effects
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Electrophoretic Mobility Shift Assay
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Flow Cytometry
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Humans
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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Luciferases / genetics
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Plasmids
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Promoter Regions, Genetic
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RNA, Small Interfering / genetics
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Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics*
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Reverse Transcriptase Polymerase Chain Reaction
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Sp1 Transcription Factor / metabolism*
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TNF-Related Apoptosis-Inducing Ligand / pharmacology*
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TNF-Related Apoptosis-Inducing Ligand / physiology
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Transfection
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Up-Regulation
Substances
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Antineoplastic Agents
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RNA, Small Interfering
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Sp1 Transcription Factor
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Luciferases
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Capsaicin
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Calcium