| IFN-beta pretreatment sensitizes human melanoma cells to TRAIL/Apo2 ligand-induced apoptosis. | |
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MedLine Citation:
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PMID: 12097388 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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All human melanoma cell lines (assessed by annexin V and TUNEL assays) were resistant to apoptosis induction by TRAIL/Apo2L protein. TRAIL/Apo2L activated caspase-8 and caspase-3, but subsequent apoptotic events such as poly(ADP-ribose) polymerase cleavage and DNA fragmentation were not observed. To probe the molecular mechanisms of cellular resistance to apoptosis, melanoma cell lines were analyzed for expression of apoptosis regulators (apoptotic protease-associated factor-1, FLIP, caspase-8, caspase-9, caspase-3, cellular inhibitor of apoptosis, Bcl-2, or Bax); no correlation was observed. TRAIL/Apo2L was induced in melanoma cell lines by IFN-beta and had been correlated with apoptosis induction. Because IFN-beta induced other gene products that have been associated with apoptosis, it was postulated that one or more IFN-stimulated genes might sensitize cells to TRAIL/Apo2L. Melanoma cell lines were treated with IFN-beta for 16-24 h before treatment with TRAIL/Apo2L. Regardless of their sensitivity to either cytokine alone, >30% of cells underwent apoptosis in response to the combined treatment. Induction of apoptosis by IFN-beta and TRAIL/Apo2L in combination correlated with synergistic activation of caspase-9, a decrease in mitochondrial potential, and cleavage of poly(ADP-ribose) polymerase. Cleavage of X-linked inhibitor of apoptosis following IFN-beta and TRAIL/Apo2L treatment was observed in sensitive WM9, A375, or WM3211 cells but not in resistant WM35 or WM164 cells. Thus, in vitro IFN-beta and TRAIL/Apo2L combination treatment had more potent apoptotic and anti-growth effects when compared with either cytokine alone in melanoma cells lines. |
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Authors:
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Mamta Chawla-Sarkar; Douglas W Leaman; Barbara S Jacobs; Ernest C Borden |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 169 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-04 Completed Date: 2002-08-28 Revised Date: 2008-05-14 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 847-55 Citation Subset: AIM; IM |
Affiliation:
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Center for Drug Discovery and Development, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology Apoptosis / immunology* Apoptosis Regulatory Proteins Dose-Response Relationship, Immunologic Drug Combinations Drug Resistance Drug Synergism Growth Inhibitors / pharmacology Humans Hydrolysis Immunization* Interferon-alpha / pharmacology Interferon-beta / pharmacology* Ligands Melanoma / immunology*, metabolism, pathology*, therapy Membrane Glycoproteins / pharmacology* NF-kappa B / antagonists & inhibitors, metabolism Proteins / antagonists & inhibitors, metabolism Receptors, Tumor Necrosis Factor / physiology Signal Transduction / immunology TNF-Related Apoptosis-Inducing Ligand Tumor Cells, Cultured Tumor Necrosis Factor-alpha / pharmacology* X-Linked Inhibitor of Apoptosis Protein |
| Grant Support | |
ID/Acronym/Agency:
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CA 90914/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/Drug Combinations; 0/Growth Inhibitors; 0/Interferon-alpha; 0/Ligands; 0/Membrane Glycoproteins; 0/NF-kappa B; 0/Proteins; 0/Receptors, Tumor Necrosis Factor; 0/TNF-Related Apoptosis-Inducing Ligand; 0/TNFSF10 protein, human; 0/Tumor Necrosis Factor-alpha; 0/X-Linked Inhibitor of Apoptosis Protein; 0/XIAP protein, human; 0/interferon-alpha 2; 77238-31-4/Interferon-beta |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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