Mechanism of action of a new macromolecular antitumor antibiotic, C-1027

J Antibiot (Tokyo). 1990 Apr;43(4):417-21. doi: 10.7164/antibiotics.43.417.

Abstract

C-1027 is a new antitumor protein antibiotic containing a non-protein chromophore. The active moiety and the mechanism of action of this antibiotic were studied. C-1027 and its chromophore inhibited the growth of KB carcinoma and L1210 leukemia cells, even at extremely low concentrations. C-1027 inhibited DNA synthesis of L1210 cells and cleaved cellular DNA in a drug concentration-dependent manner. C-1027 and chromophore caused directly DNA single strand breaks in the purified DNA without any supplement of reducing agents. These results suggest that C-1027 chromophore may inhibit cell growth by causing DNA breakage with subsequent inhibition of DNA synthesis.

MeSH terms

  • Aminoglycosides*
  • Animals
  • Anti-Bacterial Agents*
  • Antibiotics, Antineoplastic / pharmacology*
  • Bacteriophages / genetics
  • Carcinoma
  • Carcinoma, Hepatocellular
  • Chromatophores / metabolism
  • DNA Damage*
  • DNA, Neoplasm / drug effects*
  • DNA, Superhelical / drug effects
  • DNA, Viral / drug effects
  • Enediynes
  • Humans
  • Leukemia L1210
  • Liver Neoplasms
  • Proteins / pharmacology
  • Tumor Cells, Cultured

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Antibiotics, Antineoplastic
  • DNA, Neoplasm
  • DNA, Superhelical
  • DNA, Viral
  • Enediynes
  • Proteins
  • C 1027