Document Detail

P-glycoprotein expression does not change the apoptotic pathway induced by curcumin in HL-60 cells.
MedLine Citation:
PMID:  14530869     Owner:  NLM     Status:  MEDLINE    
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.
Anna Bielak-Mijewska; Katarzyna Piwocka; Adriana Magalska; Ewa Sikora
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-10-03
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  53     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2003-12-23     Completed Date:  2004-03-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  179-85     Citation Subset:  IM    
Laboratory of Molecular Bases of Aging, Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur St, 02-093 Warsaw, Poland.
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MeSH Terms
Antineoplastic Agents / 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
P-Glycoprotein / biosynthesis*
Protein Biosynthesis
Proteins / genetics
RNA, Messenger / biosynthesis
Signal Transduction / drug effects,  physiology*
Ultraviolet Rays
Reg. No./Substance:
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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