| Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway. | |
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MedLine Citation:
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PMID: 21037225 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) can selectively trigger apoptosis in various cancer cell types. However, many cancer cells are resistant to death receptor-mediated apoptosis. Combination therapy with platinum complexes may affect TRAIL-induced signaling via modulation of various steps in apoptotic pathways. Here, we show that cisplatin or a more potent platinum(IV) complex LA-12 used in 20-fold lower concentration enhanced killing effects of TRAIL in human colon and prostate cancer cell lines via stimulation of caspase activity and overall apoptosis. Both platinum complexes increased DR5 surface expression in colon cancer cells. Small interfering RNA-mediated DR5 silencing rescued cells from sensitizing effects of platinum drugs on TRAIL-induced caspase-8 activation and apoptosis, showing the functional importance of DR5 in the effects observed. In addition, both cisplatin and LA-12 triggered the relocalization of DR4 and DR5 receptors to lipid rafts and accelerated internalization of TRAIL, which may also affect TRAIL signaling. Collectively, modulations of the initial steps of the extrinsic apoptotic pathway at the level of DR5 and plasma membrane are important for sensitization of colon and prostate cancer cells to TRAIL-induced apoptosis mediated by LA-12 and cisplatin. |
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Authors:
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Olga Vondálová Blanárová; Iva Jelínková; Arpád Szöor; Belma Skender; Karel Soucek; Viktor Horváth; Alena Vaculová; Ladislav Andera; Petr Sova; János Szöllosi; Jirina Hofmanová; György Vereb; Alois Kozubík |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-29 |
Journal Detail:
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Title: Carcinogenesis Volume: 32 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-28 Completed Date: 2011-01-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 42-51 Citation Subset: IM |
Affiliation:
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Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Czech Republic. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amantadine
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analogs & derivatives*,
pharmacology Apoptosis / drug effects*, physiology Blotting, Western Cell Line, Tumor Cell Separation Cisplatin / pharmacology* Flow Cytometry Fluorescent Antibody Technique Humans Microscopy, Confocal Neoplasms / metabolism* Organoplatinum Compounds / pharmacology* Protein Transport / drug effects RNA Interference Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects*, physiology TNF-Related Apoptosis-Inducing Ligand / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Organoplatinum Compounds; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 0/TNF-Related Apoptosis-Inducing Ligand; 0/bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV); 15663-27-1/Cisplatin; 768-94-5/Amantadine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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