The inhibition and treatment of breast cancer with poly (ADP-ribose) polymerase (PARP-1) inhibitors

Int J Biol Sci. 2006;2(4):179-85. doi: 10.7150/ijbs.2.179. Epub 2006 Jun 10.


BRCA1 and BRCA2 mutations are responsible for most familial breast carcinomas. Recent reports carried out in non-cancerous mouse BRCA1- or BRCA2-deficient embryonic stem (ES) cells, and hamster BRCA2-deficient cells have demonstrated that the targeted inhibition of poly(ADP-ribose) polymerase (PARP-1) kills BRCA mutant cells with high specificity. Although these studies bring hope for BRCA mutation carriers, the effectiveness of PARP-1 inhibitors for breast cancer remains elusive. Here we present the first in vivo demonstration of PARP-1 activity in BRCA1-deficient mammary tumors and describe the effects of PARP-1 inhibitors (AG14361, NU1025, and 3-aminobenzamide) on BRCA1-deficient ES cells, mouse and human breast cancer cells. AG14361 was highly selective for BRCA1-/- ES cells; however, NU1025 and 3-aminobenzamide were relatively non-selective. In allografts of naïve ES BRCA1-/- cells there was either partial or complete remission of tumors. However, in allografts of mouse, BRCA1-/- mammary tumors, there was no tumor regression or remission although a partial inhibition of tumor growth was observed in both the BRCA1-/- and BRCA1+/+ allografts. In human tumor cells, PARP-1 inhibitors showed no difference in vitro in limiting the growth of mammary tumors irrespective of their BRCA1 status. These results suggest that PARP-1 inhibitors may non-specifically inhibit the growth of mammary tumors.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Animals
  • BRCA1 Protein / deficiency*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / deficiency*
  • BRCA2 Protein / genetics
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Division
  • Cricetinae
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Genetic Carrier Screening
  • Germ-Line Mutation
  • Humans
  • Mastectomy
  • Mice
  • Ovarian Neoplasms / genetics
  • Ovariectomy
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Stem Cells / drug effects
  • Transcription, Genetic
  • Transplantation, Heterologous
  • Transplantation, Homologous


  • BRCA1 Protein
  • BRCA2 Protein
  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1