Chivosazoles A and F, cytostatic macrolides from myxobacteria, interfere with actin.
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.
Diestel
Randi
R
Abteilung Chemische Biologie, Helmholtz-Zentrum für Infektionsforschung, Braunschweig, Germany.
Irschik
Herbert
H
Jansen
Rolf
R
Khalil
Mohammed W
MW
Reichenbach
Hans
H
Sasse
Florenz
F
D008841:Actin Cytoskeleton / Q000187:drug effects*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D016195:G2 Phase; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D005810:Multigene Family; D009231:Myxococcales / Q000737:chemistry*
D000199:Actins; D018942:Macrolides; C096623:chivosazol A; C547318:chivosazole F