Potentiation of the antitumor activity of cisplatin in mice by 3-aminobenzamide and nicotinamide

Cancer Chemother Pharmacol. 1988;22(4):303-7. doi: 10.1007/BF00254236.

Abstract

3-Aminobenzamide (3AB) and nicotinamide (NA), inhibitors of adenosine-ribose transferase (ADPRT), potentiated the antitumor activity of cisplatin (DDP) on Ehrlich ascites carcinoma in mice. The mean survival times of the mice increased from 21.2-37.0 days in DDP-treated groups to 47.0-54.6 days in mice treated with DDP plus NA or 3AB. These drugs also potentiated DDP antitumor activity on sarcoma 180, with the inhibition rates increasing from 12.4%-20.8% in groups treated daily with DDP to 29.8%-46.4% in those treated with DDP plus NA or 3AB; however, neither 3AB nor NA alone showed any antitumor activity. The single-dose lethality of DDP on mice was partially reversed by either NA or 3AB. The pathological study revealed that the morphologic changes in the proximal tubules 1 month after a single dose of DDP (10 mg/kg) were partially prevented by a single protective dose (5 mmol/kg) of NA or 3AB. Our results suggest that the combination of DDP with ADPRT inhibitors might be used clinically in the future.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols*
  • Benzamides / pharmacology*
  • Carcinoma, Ehrlich Tumor / pathology
  • Cisplatin / pharmacology*
  • Drug Synergism
  • Female
  • Male
  • Mice
  • Necrosis
  • Niacinamide / pharmacology*
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Sarcoma 180 / pathology

Substances

  • Benzamides
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Niacinamide
  • 3-aminobenzamide
  • Cisplatin