Inhibition of proliferation and invasiveness of ovarian cancer C13* cells by a poly(ADP-ribose) polymerase inhibitor and the role of nuclear factor-κB

J Int Med Res. 2013 Oct;41(5):1577-85. doi: 10.1177/0300060513480913.

Abstract

Objective: To investigate the effect of the poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor PJ34 on the proliferation and invasiveness of ovarian cancer C13* cells and the role of nuclear factor-κB (NF-κB).

Methods: Proliferation of C13* cells was measured using a 3 -(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide assay after incubation with PJ34 at different concentrations and for different treatment durations. In addition, expression of PARP-1 and the NF-κB p65 subunit after treatment with PJ34 was measured using Western blot and immunocytochemistry. The effect of PJ34 on cell invasiveness was examined using a transwell invasion assay.

Results: PJ34 inhibited proliferation of C13* cells in a time- and dose-dependent manner. PJ34 treatment was also associated with a dose-dependent decrease in PARP-1 and NF-κB p65 expression and attenuated invasiveness of C13* cells. PARP-1 expression was positively correlated with NF-κB p65 expression.

Conclusion: The PARP-1 inhibitor PJ34 can markedly inhibit the proliferation and invasiveness of C13* cells, possibly due to PARP-1-mediated attenuation of NF-κB activity.

Keywords: PJ34; Poly(ADP-ribose) polymerase-1; invasiveness; nuclear factor-κB; ovarian cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Diffusion Chambers, Culture
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Gene Expression
  • Humans
  • Phenanthrenes / pharmacology*
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism
  • Time Factors
  • Transcription Factor RelA / antagonists & inhibitors*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
  • Phenanthrenes
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Transcription Factor RelA
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases