title: PSC 833 modulation of multidrug resistance to paclitaxel in cultured human ovarian carcinoma cells leads to apoptosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovakia. exondura@savba.sk
authors.forename: Jozef
authors.initials: J
authors.lastname: Duraj
authors.forename: Jan
authors.initials: J
authors.lastname: Sedlak
authors.forename: Juraj
authors.initials: J
authors.lastname: Bies
authors.forename: Jana
authors.initials: J
authors.lastname: Chovancova
authors.forename: Branko
authors.initials: B
authors.lastname: Chorvath
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D003524:Cyclosporins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D017239:Paclitaxel; C070272:valspodar