Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells
Identifieur interne : 002A64 ( Ncbi/Curation ); précédent : 002A63; suivant : 002A65Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells
Auteurs : Dae-Hee Lee [États-Unis] ; Dong-Wook Kim [États-Unis] ; Chang-Hwa Jung [Corée du Sud] ; Yong J. Lee [États-Unis] ; Daeho Park [Corée du Sud]Source :
- Toxicology and applied pharmacology [ 0041-008X ] ; 2014.
Descripteurs français
- KwdFr :
- Alcools gras (pharmacologie), Antinéoplasiques d'origine végétale (pharmacologie), Apoptose (), Astrocytes (), Caspase-3 (métabolisme), Caspase-7 (métabolisme), Catéchols (pharmacologie), Espèces réactives de l'oxygène (métabolisme), Glioblastome (anatomopathologie), Humains, Ligand TRAIL (toxicité), Lignée cellulaire tumorale, Petit ARN interférent (pharmacologie), Protéines proto-oncogènes c-bcl-2 (métabolisme), Protéines régulatrices de l'apoptose (métabolisme), Récepteurs au TRAIL (biosynthèse).
- MESH :
- anatomopathologie : Glioblastome.
- biosynthèse : Récepteurs au TRAIL.
- métabolisme : Caspase-3, Caspase-7, Espèces réactives de l'oxygène, Protéines proto-oncogènes c-bcl-2, Protéines régulatrices de l'apoptose.
- pharmacologie : Alcools gras, Antinéoplasiques d'origine végétale, Catéchols, Petit ARN interférent.
- toxicité : Ligand TRAIL.
- Apoptose, Astrocytes, Humains, Lignée cellulaire tumorale.
English descriptors
- KwdEn :
- Antineoplastic Agents, Phytogenic (pharmacology), Apoptosis (drug effects), Apoptosis Regulatory Proteins (metabolism), Astrocytes (drug effects), Caspase 3 (metabolism), Caspase 7 (metabolism), Catechols (pharmacology), Cell Line, Tumor, Fatty Alcohols (pharmacology), Glioblastoma (pathology), Humans, Proto-Oncogene Proteins c-bcl-2 (metabolism), RNA, Small Interfering (pharmacology), Reactive Oxygen Species (metabolism), Receptors, TNF-Related Apoptosis-Inducing Ligand (biosynthesis), TNF-Related Apoptosis-Inducing Ligand (toxicity).
- MESH :
- chemical , biosynthesis : Receptors, TNF-Related Apoptosis-Inducing Ligand.
- chemical , metabolism : Apoptosis Regulatory Proteins, Caspase 3, Caspase 7, Proto-Oncogene Proteins c-bcl-2, Reactive Oxygen Species.
- chemical , pharmacology : Antineoplastic Agents, Phytogenic, Catechols, Fatty Alcohols, RNA, Small Interfering.
- drug effects : Apoptosis, Astrocytes.
- pathology : Glioblastoma.
- chemical , toxicity : TNF-Related Apoptosis-Inducing Ligand.
- Cell Line, Tumor, Humans.
Abstract
Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS).We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy.
Url:
DOI: 10.1016/j.taap.2014.06.030
PubMed: 25034532
PubMed Central: 4295120
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PMC:4295120Le document en format XML
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<term>Apoptosis Regulatory Proteins (metabolism)</term>
<term>Astrocytes (drug effects)</term>
<term>Caspase 3 (metabolism)</term>
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<term>RNA, Small Interfering (pharmacology)</term>
<term>Reactive Oxygen Species (metabolism)</term>
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<term>Antinéoplasiques d'origine végétale (pharmacologie)</term>
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<term>Astrocytes ()</term>
<term>Caspase-3 (métabolisme)</term>
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<term>Catéchols (pharmacologie)</term>
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<term>Protéines régulatrices de l'apoptose (métabolisme)</term>
<term>Récepteurs au TRAIL (biosynthèse)</term>
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<term>RNA, Small Interfering</term>
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<term>Protéines proto-oncogènes c-bcl-2</term>
<term>Protéines régulatrices de l'apoptose</term>
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<front><div type="abstract" xml:lang="en"><p id="P1">Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS).We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy.</p>
</div>
</front>
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