| P-glycoprotein expression does not change the apoptotic pathway induced by curcumin in HL-60 cells. | |
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MedLine Citation:
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PMID: 14530869 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: One of the mechanisms responsible for the multidrug resistance (MDR) phenotype of cancer cells is overexpression of so-called ATP-dependent drug efflux proteins: the 170-kDa P-glycoprotein (P-gp) encoded by the MDR1 gene and the 190-kDa multidrug resistance-associated protein 1 encoded by the MRP1 gene. The purpose of the present study was to verify the hypothesis postulating that P-gp expression, apart from enabling drug efflux, confers on the cells resistance to apoptosis by inhibiting caspase-8 and caspase-3. MATERIALS AND METHODS: Human HL-60 cells, either drug-sensitive or with the MDR phenotype caused by overexpression of P-gp (HL-60/Vinc) or MRP1 (HL-60/Adr), were treated with the natural dye curcumin at 50 micro M or with UVC to induce apoptosis. Symptoms of cell death were assessed by morphological observation after Hoechst staining, DNA fragmentation was measured by flow cytometry and the TUNEL method, and caspase-8 and caspase-3 activation and cytochrome c release from mitochondria were measured by Western blotting. RESULTS: Curcumin induced cell death in HL-60 cells, both sensitive and with the MDR phenotype, which could be classified as caspase-3-dependent apoptosis, together with cytochrome c release, activation of caspase-3 and oligonucleosomal DNA fragmentation. No active caspase-8 was detected. Also UVC caused caspase-3 activation in both the sensitive and the MDR HL-60 cells. CONCLUSIONS: Our findings show that there was no correlation between P-gp expression and resistance to caspase-3-dependent apoptosis induced by curcumin and UVC, at least in HL-60 cells. However, we cannot exclude the possibility of parallel P-gp expression and caspase-3 inhibition in some other cell lines, as cancer cells can acquire many different apoptosis-resistance mechanisms. |
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Authors:
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Anna Bielak-Mijewska; Katarzyna Piwocka; Adriana Magalska; Ewa Sikora |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-10-03 |
Journal Detail:
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Title: Cancer chemotherapy and pharmacology Volume: 53 ISSN: 0344-5704 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 2004 Feb |
Date Detail:
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Created Date: 2003-12-23 Completed Date: 2004-03-09 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 179-85 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Bases of Aging, Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur St, 02-093 Warsaw, Poland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis / drug effects, physiology* Blotting, Western Caspase 3 Caspase 8 Caspases / biosynthesis Curcumin / pharmacology* Cytochromes c / biosynthesis, genetics Enzyme Activation / drug effects, radiation effects Flow Cytometry Gene Expression / drug effects Genes, MDR / genetics HL-60 Cells Humans P-Glycoprotein / biosynthesis* Protein Biosynthesis Proteins / genetics RNA, Messenger / biosynthesis Signal Transduction / drug effects, physiology* Ultraviolet Rays |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/P-Glycoprotein; 0/Proteins; 0/RNA, Messenger; 458-37-7/Curcumin; 9007-43-6/Cytochromes c; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/CASP8 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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