Jasplakinolide, a cytotoxic and antiproliferative natural product from marine sponge, has been shown to induce the polymerization of actin, stabilize filaments and compete with phalloidin for binding to F-actin with a Kd of about 15 nM. Swinholide A, a fungicidal and cytotoxic natural product from another marine sponge, has been shown to cause cells in culture to round up, lose stress fibers and lamellipodia and inhibit cytokinesis but not nuclear division. In vitro swinholide A severs, but does not cap, and rapidly depolymerizes actin filaments forming a stable, non-polymerizable 1:1 complex with actin dimer with a Kd about 25 nM. The observation that muscle F-actin depolymerizes when added to extracts of Acanthamoeba castellanii while Acanthamoeba is stable seems to depend on the actions of two factors that have been partially purified: an ATP- sensitive filament stabilizing protein and a depolymerizing protein that has been partially purified. Presumably, one or both of these proteins interacts differently with muscle and amoeba F-actin but this has not yet been determined.
