ROLE OF PRONASE-RESISTANT PEPTIDE SEGMENTS OF THE ANTITUMOR PROTEIN ANTIBIOTICS, AUROMOMYCIN AND MACROMOMYCIN, IN STABILIZING CYTOCIDAL ACTIVITY OF THE CHROMOPHORE MOIETIES TO CARCINOMA CELLS

The free chromophores isolated from the antitumor protein antibiotics, auromomycin (AUR) and macromomycin (MCR), were rapidly inactivated by incubation in serum-containing medium at 37°C in the dark with respect to cytocidal activity to human lung carcinoma A549 cells. Under the same conditions, the...

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Bibliographic Details
Published in:Journal of antibiotics 1983, Vol.36(6), pp.721-727
Main Authors: MIWA, NOBUHIKO, MIZUNO, SATOSHI, OKAMOTO, SUEHIKO
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents
Antibiotics, Antineoplastic - toxicity
Cell Line
Cell Survival - drug effects
Cell Transformation, Neoplastic
Humans
Kinetics
Lung - drug effects
Lung - embryology
Lung Neoplasms - physiopathology
Peptides - toxicity
Pronase
Simian virus 40 - genetics
Structure-Activity Relationship
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Summary:The free chromophores isolated from the antitumor protein antibiotics, auromomycin (AUR) and macromomycin (MCR), were rapidly inactivated by incubation in serum-containing medium at 37°C in the dark with respect to cytocidal activity to human lung carcinoma A549 cells. Under the same conditions, the intact antibiotics, their pronase-hydrolysates and reconstituents from the Chromophores and apo-proteins were stable. IntaCt and reconstituted AUR and MCR were more resistant to pronase digestion than the apo-proteins. The analyses of the pronase-hydrolysates of AUR and MCR by SDS-polyacrylamide gel electrophoresis and ultrafiltration showed that the antibiotics (13 kilodaltons (kDa)) were degraded to produce peptide fragments (1-3 kDa) in which most cytotoxicity of the pronase-hydrolysates resided. The pronase-hydrolysates exhibited a differential cytocidal activity to normal diploid fibroblasts (WI38), their SV40-transformants (VA13) and carcinoma cells (A549) of human lung origin as was observed for the intact antibiotics. These results indicate that specificinteraction between the chromophores and the pronaseresistant peptide segments (1-3 kDa) of the protein moiety stabilizes the cytocidal activity of the chromophores and also protects the peptide segments from pronase digestion.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.36.721