Inhibition of poly(ADP-ribose) polymerase (PARP) induces apoptosis in lung cancer cell lines

Cancer Invest. 2011 Nov;29(9):608-16. doi: 10.3109/07357907.2011.621916.

Abstract

We have tested PJ34, a potent inhibitor of poly(ADP-ribose) polymerase (PARP), against various lung cancer cell lines (Calu-6, A549, and H460) and normal human bronchial epithelial cells (HBECs). While using WST1 dye assay, lung cancer cells exhibited LD(50) values of approximately 30 μM PJ34 (72-hr assay). Molecular data showed that the effect of PJ34-induced apoptosis on lung cancer cells occurs via a caspase-dependent pathway. The present study has clearly shown that (a) PARP inhibitor can independently kill tumor cells, (b) caspase-3 has modest influence on PARP-inhibitor-mediated cancer-specific toxicity, and (c) a pan-caspase inhibitor decreases the apoptotic effect of PJ34.

MeSH terms

  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Caspase Inhibitors
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology*
  • Phenanthrenes / pharmacology*
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Poly(ADP-ribose) Polymerases / metabolism

Substances

  • Caspase Inhibitors
  • Enzyme Inhibitors
  • N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride
  • Phenanthrenes
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases
  • Caspase 3