Action of tolytoxin on cell morphology, cytoskeletal organization, and actin polymerization

Abstract

Tolytoxin, a cytostatic, antifungal macrolide produced by blue-green algae of the genus Scytonema, is a potent, reversible inhibitor of cytokinesis in cultured mammalian cells. Treatment of KB cells with 2-16 nM tolytoxin results in profound morphological changes, beginning with the formation of zeiotic processes and culminating in nuclear protrusion. In L1210 cells, cytokinesis is inhibited by as little as 2 nM tolytoxin, while karyokinesis proceeds normally, resulting in polynucleation. Tolytoxin specifically disrupts microfilament organization in A10 cells, while having no apparent effect on microtubules or intermediate filaments. Tolytoxin inhibited actin polymerization in vitro and also caused the depolymerization or fragmentation of F-actin in vitro. Tolytoxin exhibits effects that closely resemble those of cytochalasin B but is effective at concentrations 1/50-1/1,000 that of cytochalasin B.

The Multiple Roles of Cyk1p in the Assembly and Function of the Actomyosin Ring in Budding Yeast

“…The force that drives the membrane constriction is thought to come from the mechanochemistry that occurs within an actomyosin-based contractile ring (reviewed in Schroeder, 1990;Fishkind and Wang, 1995). Although a myosin II independent mechanism may also exist to drive membrane constriction (Neujahr et al, 1997), the importance of myosin II and actin filaments in cleavage furrow formation and progression is supported by several studies involving inhibitors of actin and myosin in dividing eggs and cultured cells (Zurek et al, 1990;Patterson et al, 1993) as well as genetic manipulations in Dictyostelium and yeast (De Lozanne and Spudich, 1987;Knecht and Loomis, 1987;Watts et al, 1987;Kitayama et al, 1997) The contractile ring is a transient structure whose assembly and disassembly are under stringent temporal and spatial regulation. The molecular mechanisms for actin and myosin II recruitment to the cleavage furrow are not known.…”

Cellular Changes of Rat Embryonic Fibroblasts by an Actin-Polymerization Inhibitor, Bistheonellide A, from a Marine Sponge.

“…Latrunculin (6), mycalorides (7), swinholides (8,9), and bistheonellides (10) have been isolated from marine sponges and found to disrupt actin filaments (ll, 12, 13, 14, 15). Tolytoxin, which has similar functions and structures, has been isolated from cyanobacteria (16). The agents in this group bind an actin monomer or dimer, and someof themsever actin filaments that form such small complexesas monomers or dimers.…”

Seaweed resistance to microbial attack: A targeted chemical defense against marine fungi

“…Error bars depict Ϯ one standard error. IC 50 values were determined (in triplicate) in a similar manner except 1-ml equivalents were solubilized in acetone and serially diluted 1:1 with sterile seawater to a total volume of 500 l. Five hundred microliters of 2ϫ molten medium was then added to each well, the wells were inoculated, and the dilution at which fungal growth was inhibited by 50% relative to controls was determined.…”

“…The antineoplastic (anticancer) activity of 1 was of a similar magnitude to the swinholide and tolytoxin͞scytophycin classes of compounds (41,48,49), although this comparison is potentially confounded by the use of different human cancer cell lines. The tolytoxin͞scytophycin group inhibits actin polymerization (50,51), and because of the structural similarity of 1 and 2, it is possible that 1 acts by a similar mechanism. Although L. variegata has been the subject of several earlier chemical studies, 1 was not previously discov- (Table 1) correspond to 1 ϫ 10 Ϫ5 percent and 4 ϫ 10 Ϫ5 percent of plant dry mass, respectively.…”