Document Detail


PSC 833 modulation of multidrug resistance to paclitaxel in cultured human ovarian carcinoma cells leads to apoptosis.
MedLine Citation:
PMID:  12530099     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Multidrug resistance (MDR) modulator PSC 833 has been shown to modulate multidrug resistance in Pg-p-positive human ovarian carcinoma cells A2780/ADR. Co-treatment of A2780/ADR cells with paclitaxel (PTX) and PSC 833 resulted in the restoration of PTX-sensitivity comparable to that in parental A2780 cells. RESULTS: The flow cytometry experiments presented here showed PTX-(A2780) and PTX plus PSC 833 (A2780/ADR)-induced cell accumulation in the G2/M-phase of the cell cycle with concomitant appearance of apoptotic cells with sub-G0 (hypodiploid) DNA content. Furthermore, these events were accompanied by the appearance of poly(ADP-ribose) polymerase (PARP) cleavage, up-regulation of Bax, p53 and p21WAF1/CIP1 proteins and internucleosomal DNA fragmentation. Interestingly, we did not detect any significant alterations in Bcl-xL, CD95/Fas and Fas-L protein levels. CONCLUSION: These results demonstrate the PSC 833 reduced the Pg-p-mediated multidrug resistance in human ovarian carcinoma cells to PTX-induced apoptosis in vitro.
Authors:
Jozef Duraj; Jan Sedlak; Juraj Bies; Jana Chovancova; Branko Chorvath
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  22     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2002 Nov-Dec
Date Detail:
Created Date:  2003-01-17     Completed Date:  2003-01-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3425-8     Citation Subset:  IM    
Affiliation:
Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovakia. exondura@savba.sk
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects
Blotting, Western
Cell Cycle / drug effects
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / biosynthesis
Cyclosporins / administration & dosage,  pharmacology*
Drug Resistance, Multiple*
Drug Resistance, Neoplasm
Drug Synergism
Female
Humans
Ovarian Neoplasms / drug therapy*,  metabolism
Paclitaxel / administration & dosage,  pharmacology*
Proto-Oncogene Proteins / biosynthesis
Proto-Oncogene Proteins c-bcl-2*
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / biosynthesis
Up-Regulation / drug effects
bcl-2-Associated X Protein
Chemical
Reg. No./Substance:
0/BAX protein, human; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Cyclosporins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 121584-18-7/valspodar; 33069-62-4/Paclitaxel

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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