title: Combinatorial effects of PARP inhibitor PJ34 and histone deacetylase inhibitor vorinostat on leukemia cell lines.
abstract: BACKGROUND
  Poly (ADP-ribose) polymerase (PARP) inhibitors and histone deacetylase (HDAC) inhibitors are new promising anticancer drugs. The aim of the present study was to investigate the effect of combination treatment with PARP inhibitor PJ34 and HDAC inhibitor vorinostat on human leukemia cell lines.
  
  
  METHODS
  Proliferation, apoptosis, mitochondrial membrane potential (ψm) and cell cycle were assessed in HL60, MOLT4, U937 and K562 cells cultured with each drug alone and with both drugs.
  
  
  RESULTS
  PJ34 alone at 0.2-0.4 μM did not influence the examined parameters. Vorinostat alone at 1.0-2.5 μM reduced proliferation, increased apoptosis rate, lowered ψm and increased the percentage of sub-G1 cells in all cell lines. Incubation with both drugs caused further inhibition of proliferation and increase in apoptosis associated with a decrease in ψm and sub-G1 arrest in HL60, MOLT4 and K562 cells, but not in U937 cells.
  
  
  CONCLUSIONS
  Combination of PARP and HDAC inhibitors can exert a synergistic effect on inhibition of proliferation and increase apoptosis of leukemia cells.
authors.affiliation: Department of Histology, Jagiellonian University Medical College, Kopernika 7, PL-31034 Krakow, Poland. ejasek@cm-uj.krakow.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jasek
authors.forename: Mariusz
authors.initials: M
authors.lastname: Gajda
authors.forename: Grzegorz J
authors.initials: GJ
authors.lastname: Lis
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jasińska
authors.forename: Jan A
authors.initials: JA
authors.lastname: Litwin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020014:K562 Cells; D007938:Leukemia; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D020298:U937 Cells; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000077337:Vorinostat
keywords: HDAC inhibitors; PARP inhibitors; PJ34; apoptosis; cell cycle; leukemia cell lines; vorinostat