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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
1997-9-24
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pubmed:abstractText |
Anticancer agents have been shown to trigger apoptosis in chemosensitive tumors such as neuroblastomas. We previously identified activation of the CD95 system as one of the key mechanisms for doxorubicin-induced apoptosis in leukemic T cells. Here, we report that therapeutic concentrations of doxorubicin, cisplatinum, and VP-16 led to induction of CD95 receptor and CD95 ligand (CD95-L) that mediated cell death in chemosensitive neuroblastoma cells. Using F(ab')2 anti-CD95 antibody fragments to interfere with CD95-L-receptor interaction markedly reduced apoptosis induced by those drugs in vitro. Cyclosporin A inhibited induction of CD95 mRNA and CD95-L mRNA and blocked drug-mediated apoptosis. Drug-induced apoptosis involved activation of caspases (interleukin 1beta-converting enzyme/Ced-3-like proteases) and processing of the prototype caspase substrate PARP and was completely blocked by benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a peptide inhibitor of caspases. In addition, neuroblastoma cells that were resistant to CD95-triggered apoptosis also displayed cross-resistance to chemotherapeutic agents. These data provide new clues for understanding the molecular requirements for drug-induced apoptosis in chemosensitive neuroblastoma cells by demonstrating that cell death was mediated via the CD95-L-receptor system and may open new avenues for targeting drug resistance of neuroblastoma.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
57
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3823-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9288794-Antigens, CD95,
pubmed-meshheading:9288794-Antineoplastic Agents,
pubmed-meshheading:9288794-Apoptosis,
pubmed-meshheading:9288794-Cisplatin,
pubmed-meshheading:9288794-Cyclosporine,
pubmed-meshheading:9288794-Cysteine Endopeptidases,
pubmed-meshheading:9288794-DNA Fragmentation,
pubmed-meshheading:9288794-Doxorubicin,
pubmed-meshheading:9288794-Drug Resistance, Neoplasm,
pubmed-meshheading:9288794-Enzyme Activation,
pubmed-meshheading:9288794-Etoposide,
pubmed-meshheading:9288794-Fas Ligand Protein,
pubmed-meshheading:9288794-Humans,
pubmed-meshheading:9288794-Immunoglobulin Fragments,
pubmed-meshheading:9288794-Immunosuppressive Agents,
pubmed-meshheading:9288794-Membrane Glycoproteins,
pubmed-meshheading:9288794-Neuroblastoma,
pubmed-meshheading:9288794-RNA, Messenger,
pubmed-meshheading:9288794-Tumor Cells, Cultured,
pubmed-meshheading:9288794-Up-Regulation
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pubmed:year |
1997
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pubmed:articleTitle |
The CD95 (APO-1/Fas) system mediates drug-induced apoptosis in neuroblastoma cells.
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pubmed:affiliation |
Division of Hematology/Oncology, University Children's Hospital, German Cancer Research Center, Heidelberg.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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