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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1999-2-18
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pubmed:abstractText |
A major problem with treating patients with cancer by traditional chemotherapeutic regimes is that their tumors often develop a multidrug resistant (MDR) phenotype and subsequently become insensitive to a range of different chemotoxic drugs. One cause of MDR is overexpression of the drug-effluxing protein, P-glycoprotein. It is now apparent that P-glycoprotein may also possess a more generic antiapoptotic function that protects P-glycoprotein-expressing cancer cells and normal cells from cell death. Herein we show that cells induced to express P-glycoprotein either by drug selection or by retroviral gene transduction with MDR1 cDNA are resistant to cell death induced by a wide range of death stimuli, such as FasL, tumor necrosis factor (TNF), and ultraviolet (UV) irradiation, that activate the caspase apoptotic cascade.However, P-glycoprotein-expressing cells were not resistant to caspase-independent cell death mediated by pore-forming proteins and granzyme B.MDR P-glycoprotein-expressing cells were made sensitive to caspase-dependent apoptosis by the addition of anti-P-glycoprotein antibodies or verapamil, a pharmacological inhibitor of P-glycoprotein function. Clonogenic assays showed that P-glycoprotein confers long-term resistance to caspase-dependent apoptotic stimuli but not to caspase-independent cell death stimuli. This study has confirmed a potential novel physiological function for P-glycoprotein and it now remains to dissect the molecular mechanisms involved in the inhibition of capsase-dependent cell death by P-glycoprotein.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
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/GZMB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Granzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Perforin,
http://linkedlifedata.com/resource/pubmed/chemical/Pore Forming Cytotoxic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Verapamil,
http://linkedlifedata.com/resource/pubmed/chemical/Vinblastine
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-4971
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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 |
93
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1075-85
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9920858-Antibodies, Monoclonal,
pubmed-meshheading:9920858-Antigens, CD95,
pubmed-meshheading:9920858-Antineoplastic Agents,
pubmed-meshheading:9920858-Apoptosis,
pubmed-meshheading:9920858-Caspases,
pubmed-meshheading:9920858-Cytotoxicity, Immunologic,
pubmed-meshheading:9920858-DNA, Complementary,
pubmed-meshheading:9920858-Dexamethasone,
pubmed-meshheading:9920858-Enzyme Inhibitors,
pubmed-meshheading:9920858-Etoposide,
pubmed-meshheading:9920858-Fas Ligand Protein,
pubmed-meshheading:9920858-Genes, MDR,
pubmed-meshheading:9920858-Granzymes,
pubmed-meshheading:9920858-Humans,
pubmed-meshheading:9920858-Leukemia-Lymphoma, Adult T-Cell,
pubmed-meshheading:9920858-Membrane Glycoproteins,
pubmed-meshheading:9920858-Neoplasm Proteins,
pubmed-meshheading:9920858-P-Glycoprotein,
pubmed-meshheading:9920858-Perforin,
pubmed-meshheading:9920858-Pore Forming Cytotoxic Proteins,
pubmed-meshheading:9920858-Recombinant Proteins,
pubmed-meshheading:9920858-Serine Endopeptidases,
pubmed-meshheading:9920858-Transfection,
pubmed-meshheading:9920858-Tumor Necrosis Factor-alpha,
pubmed-meshheading:9920858-Tumor Stem Cell Assay,
pubmed-meshheading:9920858-Ultraviolet Rays,
pubmed-meshheading:9920858-Verapamil,
pubmed-meshheading:9920858-Vinblastine
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pubmed:year |
1999
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pubmed:articleTitle |
P-glycoprotein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death.
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pubmed:affiliation |
The Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia. r.johnstone@ari.unimelb.edu.au
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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