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Chivosazoles A and F, cytostatic macrolides from myxobacteria, interfere with actin
Randi Diestel1, Herbert Irschik, Rolf Jansen
1Abteilung Chemische Biologie, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany.
Abstract:
Chivosazoles A and F, isolated from Sorangium cellulosum, showed high antiproliferative activity with different mammalian cell lines including human cancer cells. The chivosazoles caused a delay in G2/M phase of the cell cycle, and treated cells often contained two nuclei. By labeling F-actin it was shown that the actin cytoskeleton of the cells starts to break down after a few minutes of treatment. In vitro polymerization assays with purified G-actin revealed that the chivosazoles inhibit actin polymerization and also cause a depolymerization of pyrene-labeled F-actin microfilaments prepared in vitro. Chivosazoles are new tools for the investigation of issues concerning the actin cytoskeleton and they have a different mode of action from the known microfilament-disrupting compounds like rhizopodin and cytochalasin D.
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