Mechanism of action of a new macromolecular antitumor antibiotic, C-1027.
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.
Sugimoto
Y
Y
Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Otani
T
T
Oie
S
S
Wierzba
K
K
Yamada
Y
Y
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001435:Bacteriophages / Q000235:genetics; D002277:Carcinoma; D006528:Carcinoma, Hepatocellular; D002856:Chromatophores / Q000378:metabolism; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects*; D004278:DNA, Superhelical / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D053281:Enediynes; D006801:Humans; D007939:Leukemia L1210; D008113:Liver Neoplasms; D011506:Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D004278:DNA, Superhelical; D004279:DNA, Viral; D053281:Enediynes; D011506:Proteins; C058024:C 1027