Synergistic cytotoxic effect of tiazofurin and ribavirin in hepatoma cells

Biochem Biophys Res Commun. 1988 May 31;153(1):321-7. doi: 10.1016/s0006-291x(88)81225-7.

Abstract

Tiazofurin, an anti-cancer drug, which induces remissions in human leukemia, and ribavirin, an anti-viral agent, bind at separate sites (NADH and IMP-XMP sites, respectively) on the target enzyme, IMP dehydrogenase. Now we show that the binding to IMP dehydrogenase of these drugs at two separate sites is translated into synergistic inhibition of de novo guanylate biosynthesis and synergistic toxicity in rat hepatoma 3924A cells. These results may be utilized in the chemotherapy of neoplastic diseases and in the treatment of hepatitis virus infection and hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Drug Synergism
  • Guanosine Monophosphate / biosynthesis
  • IMP Dehydrogenase / metabolism
  • Liver Neoplasms, Experimental / pathology*
  • Organoselenium Compounds*
  • Purines / biosynthesis
  • Rats
  • Ribavirin / analogs & derivatives
  • Ribavirin / pharmacology*
  • Ribonucleosides / pharmacology*
  • Selenium / pharmacology

Substances

  • Organoselenium Compounds
  • Purines
  • Ribonucleosides
  • Ribavirin
  • Guanosine Monophosphate
  • IMP Dehydrogenase
  • Selenium
  • selenazofurin
  • tiazofurin