| 5-fluorouracil-induced death of Jurkat T-cells--a role for caspases and MCL-1. | |
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MedLine Citation:
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PMID: 21036698 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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5-Fluorouracil (5-FU) is frequently used in cancer treatment. Previous studies with 5-FU suggest that proapoptotic protein BAX and tumor suppressor protein TP53 are central factors in this process. As the leukemic T cell line Jurkat E6 has mutations in both these genes, we investigated a possible activation of alternative death pathways following 5-FU treatment. Here we show that 5-FU triggers apoptosis in Jurkat cells in a dose-dependent manner. Death responses were only moderately attenuated in the presence of a general caspase inhibitor. However, flow cytometric analysis showed activation of caspase 3 and a slight increase in ROS generation in a time- and dose-dependent manner. Furthermore, we observed 5-FU induced PARP cleavage and notably, reduced expression of antiapoptotic MCL-1L associated with the appearance of proapoptotic MCL-1S. Our results demonstrate the activation of alternative death pathways following treatment with 5-FU, despite mutations in the TP53 and BAX genes. |
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Authors:
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Dina M Aresvik; Rolf D Pettersen; Tore G Abrahamsen; Marianne S Wright |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anticancer research Volume: 30 ISSN: 1791-7530 ISO Abbreviation: Anticancer Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2010-12-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 3879-87 Citation Subset: IM |
Affiliation:
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Department of Paediatric Research, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway. Dina.Aresvik@rr-research.no |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Antimetabolites, Antineoplastic / pharmacology* Apoptosis / drug effects Caspase 3 / antagonists & inhibitors, metabolism* Cell Death / drug effects*, physiology Cysteine Proteinase Inhibitors / pharmacology Enzyme Activation / drug effects Fluorouracil / pharmacology* Humans Jurkat Cells Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / biosynthesis, metabolism* T-Lymphocytes / drug effects*, enzymology, metabolism*, pathology |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Antimetabolites, Antineoplastic; 0/Cysteine Proteinase Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 0/myeloid cell leukemia sequence 1 protein; 51-21-8/Fluorouracil; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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