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https://ahro.austin.org.au/austinjspui/handle/1/13643
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DC Field | Value | Language |
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dc.contributor.author | Johnstone, R W | en |
dc.contributor.author | Cretney, E | en |
dc.contributor.author | Smyth, Mark J | en |
dc.date.accessioned | 2015-05-16T03:31:19Z | |
dc.date.available | 2015-05-16T03:31:19Z | |
dc.date.issued | 1999-02-01 | en |
dc.identifier.citation | Blood; 93(3): 1075-85 | en |
dc.identifier.govdoc | 9920858 | en |
dc.identifier.other | PUBMED | en |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/13643 | en |
dc.description.abstract | 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. | en |
dc.language.iso | en | en |
dc.subject.other | Antibodies, Monoclonal.pharmacology | en |
dc.subject.other | Antigens, CD95.physiology | en |
dc.subject.other | Antineoplastic Agents.pharmacology | en |
dc.subject.other | Apoptosis.drug effects.physiology.radiation effects | en |
dc.subject.other | Caspases.physiology | en |
dc.subject.other | Cytotoxicity, Immunologic | en |
dc.subject.other | DNA, Complementary.genetics | en |
dc.subject.other | Dexamethasone.pharmacology | en |
dc.subject.other | Enzyme Inhibitors.pharmacology | en |
dc.subject.other | Etoposide.pharmacology | en |
dc.subject.other | Fas Ligand Protein | en |
dc.subject.other | Genes, MDR | en |
dc.subject.other | Granzymes | en |
dc.subject.other | Humans | en |
dc.subject.other | Leukemia-Lymphoma, Adult T-Cell.pathology | en |
dc.subject.other | Membrane Glycoproteins.pharmacology | en |
dc.subject.other | Neoplasm Proteins.physiology | en |
dc.subject.other | P-Glycoprotein.genetics.physiology | en |
dc.subject.other | Perforin | en |
dc.subject.other | Pore Forming Cytotoxic Proteins | en |
dc.subject.other | Recombinant Proteins.pharmacology | en |
dc.subject.other | Serine Endopeptidases.pharmacology | en |
dc.subject.other | Transfection | en |
dc.subject.other | Tumor Necrosis Factor-alpha.pharmacology | en |
dc.subject.other | Tumor Stem Cell Assay | en |
dc.subject.other | Ultraviolet Rays | en |
dc.subject.other | Verapamil.pharmacology | en |
dc.subject.other | Vinblastine.pharmacology | en |
dc.title | P-glycoprotein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death. | en |
dc.type | Journal Article | en |
dc.identifier.journaltitle | Blood | en |
dc.identifier.affiliation | The Austin Research Institute, Austin Hospital, Heidelberg, Victoria, Australia | en |
dc.description.pages | 1075-85 | en |
dc.relation.url | https://pubmed.ncbi.nlm.nih.gov/9920858 | en |
dc.type.austin | Journal Article | en |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.languageiso639-1 | en | - |
item.openairetype | Journal Article | - |
Appears in Collections: | Journal articles |
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