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 LI 210 leukemia cells, even at extremely low concentrations. C-1027 in...

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Veröffentlicht in:	Journal of antibiotics 1990/04/25, Vol.43(4), pp.417-421
Hauptverfasser:	SUGIMOTO, YOSHIKAZU, OTANI, TOSHIO, OIE, SHINJI, WIERZBA, KONSTANTY, YAMADA, YUJI
Format:	Artikel
Sprache:	eng
Schlagworte:	Aminoglycosides Animals Anti-Bacterial Agents Antibiotics, Antineoplastic - pharmacology Antineoplastic agents Bacteriophages - genetics Biological and medical sciences Carcinoma Carcinoma, Hepatocellular Chromatophores - metabolism DNA Damage DNA, Neoplasm - drug effects DNA, Superhelical - drug effects DNA, Viral - drug effects Enediynes General aspects Humans Leukemia L1210 Liver Neoplasms Medical sciences Pharmacology. Drug treatments Proteins - pharmacology Tumor Cells, Cultured
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Beschreibung
Zusammenfassung:	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 LI 210 leukemia cells, even at extremely low concentrations. C-1027 inhibited DNA synthesis of L1210 cells and cleaved cellular DNA in a drug concentrationdependent 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.
ISSN:	0021-8820 1881-1469
DOI:	10.7164/antibiotics.43.417