title: Sulforaphane inhibits damage-induced poly (ADP-ribosyl)ation via direct interaction of its cellular metabolites with PARP-1.
abstract: METHODS
  The isothiocyanate sulforaphane, a major breakdown product of the broccoli glucosinolate glucoraphanin, has frequently been proposed to exert anticarcinogenic properties. Potential underlying mechanisms include a zinc release from Kelch-like ECH-associated protein 1 followed by the induction of detoxifying enzymes. This suggests that sulforaphane may also interfere with other zinc-binding proteins, e.g. those essential for DNA repair. Therefore, we explored the impact of sulforaphane on poly (ADP-ribose)polymerase-1 (PARP-1), poly (ADP-ribosyl)ation (PARylation), and DNA single-strand break repair (SSBR) in cell culture.
  
  
  RESULTS
  Immunofluorescence analyses showed that sulforaphane diminished H2 O2 -induced PARylation in HeLa S3 cells starting from 15 μM despite increased lesion induction under these conditions. Subcellular experiments quantifying the damage-induced incorporation of (32) P-ADP-ribose by PARP-1 displayed no direct impact of sulforaphane itself, but cellular metabolites, namely the glutathione conjugates of sulforaphane and its interconversion product erucin, reduced PARP-1 activity concentration dependently. Interestingly, this sulforaphane metabolite-induced PARP-1 inhibition was prevented by thiol compounds. PARP-1 is a stimulating factor for DNA SSBR-rate and we further demonstrated that 25 μM sulforaphane also delayed the rejoining of H2 O2 -induced DNA strand breaks, although this might be partly due to increased lesion frequencies.
  
  
  CONCLUSIONS
  Sulforaphane interferes with damage-induced PARylation and SSBR, which implies a sulforaphane-dependent impairment of genomic stability.
authors: Food Chemistry and Toxicology, Institute of Applied Bioscience, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors: Ann Liza
authors: AL
authors: Piberger
authors: Food Chemistry and Toxicology, Institute of Applied Bioscience, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors: Claudia
authors: C
authors: Keil
authors: Institute of Food Chemistry, Hamburg School of Food Science, University Hamburg, Hamburg, Germany.
authors: Stefanie
authors: S
authors: Platz
authors: Institute of Food Chemistry, Hamburg School of Food Science, University Hamburg, Hamburg, Germany.
authors: Sascha
authors: S
authors: Rohn
authors: Food Chemistry and Toxicology, Institute of Applied Bioscience, Karlsruhe Institute of Technology, Karlsruhe, Germany.
authors: Andrea
authors: A
authors: Hartwig
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D053960:DNA Breaks; D004260:DNA Repair; D006367:HeLa Cells; D006801:Humans; D017879:Isothiocyanates / Q000378:metabolism / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013454:Sulfoxides
chemical_list: D017879:Isothiocyanates; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013438:Sulfhydryl Compounds; D013454:Sulfoxides; D000246:Adenosine Diphosphate Ribose; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; C016766:sulforaphane
keywords: DNA single-strand break repair; Erucin; PARP inhibition; Sulforaphane; Thiol reactivity