Latrunculin, a new 2-thiazolidinone macrolide from the marine sponge

Kashman, Yoel; Groweiss, Amiram; Shmueli, U.

doi:10.1016/0040-4039(80)80255-3

Cited by 163 publications

(122 citation statements)

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“…Latrunculin A (Lat A) is an actin-binding marine natural product extracted from the Red Sea sponge Negombata magnifica (Kashman et al 1980) that sequesters monomeric actin in living cells (Yarmola et al 2000) and has been shown to inhibit the motility of pennate diatoms through the dissolution of the raphe-associated actin filaments (Poulsen et al 1999). Recently, Cartaxana et al (2008) have shown that Lat A is capable of inhibiting motility in cultured diatom cells while not affecting their photosynthetic activity.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting diatom motility: a new tool for the study of the photophysiology of intertidal microphytobenthic biofilms

Cartaxana

Serôdio

2008

Limnology & Ocean Methods

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The study of the photophysiology of intertidal microphytobenthos biofilms has been hampered by the confounding effects of vertical migration by motile microalgae. The present work introduces a methodology to obtain undisturbed nonmigratory biofilms, based on the diatom motility inhibitor latrunculin A (Lat A). Application of Lat A to intact sediments prevented light-induced vertical migration while not affecting the biofilm photosynthetic activity or disrupting the photic zone microenvironment. The inhibition of microalgal migration maintained the surface microalgae biomass despite exposure to stimuli that induced large migratory responses in noninhibited samples, including supersaturating irradiances or darkness. The characterization of the photophysiological responses of undisturbed biofilms without the interference of changes in surface biomass was illustrated by addressing two questions that are not possible to study on migratory biofilms with the existing methods: (i) the construction of light-response curves of steady-state photosynthetic activity, commonly used to characterize the photoacclimation status of photoautotrophs, and (ii) the characterization of the induction and relaxation kinetics of nonphotochemical quenching of in vivo fluorescence, required for the study of photoprotective processes or photoinhibition.

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Section: Introductionmentioning

confidence: 99%

Inhibiting diatom motility: a new tool for the study of the photophysiology of intertidal microphytobenthic biofilms

Cartaxana

Serôdio

2008

Limnology & Ocean Methods

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“…1 Latrunculins are reported to decrease intraocular pressure and increase outflow facility without corneal effects in monkeys.2 , 3 Latrunculin B and analogs showed antiangiogenic, antimetastatic, and antimicrobial activities. 4 The most important biological effects of latrunculins are their abilities to disrupt microfilament organization and inhibit microfilament-mediated processes without affecting the organization of the microtubular system.…”

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Latrunculin A and Its C-17-O-Carbamates Inhibit Prostate Tumor Cell Invasion and HIF-1 Activation in Breast Tumor Cells

et al. 2008

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The marine-derived macrolides latrunculins A (1) and B, from the Red Sea sponge Negombata magnifica, have been found to reversibly bind actin monomers, forming a 1:1 complex with G-actin and disrupting its polymerization. The microfilament protein actin is responsible for several essential functions within the cell such as cytokinesis and cell migration. One of the main binding pharmacophores of 1 to G-actin was identified as the C-17 lactol hydroxyl moiety that binds arginine 210 NH. Latrunculin A-17-O-carbamates 2-6 were prepared by reaction with the corresponding isocyanates. Latrunculin A (1) and carbamates 4-6 displayed potent anti-invasive activity against the human highly metastatic human prostate cancer PC-3M cells in a Matrigel™ assay at a concentration range of 50 nM-1 µM. Latrunculin A (1, 500 nM) decreased the disaggregation and cell migration of PC-3M-CT+ spheroids by three-fold. Carbamates 4 and 5 were two and half and five-fold more active than 1, respectively, in this assay with less actin binding affinity. Latrunculin A (1, IC 50 6.7 µM) and its 17-O-[N-(benzyl)carbamate (6, IC 50 29 µM) suppress hypoxia-induced HIF-1 activation in T47D breast tumor cells.Latrunculin A (1) and B are macrolides reported by Kashman and coworkers from the Red Sea sponge Negombata magnifica Kelly-Borges and Vacelet (Podospongiidae). 1 Latrunculins are reported to decrease intraocular pressure and increase outflow facility without corneal effects in monkeys.2 , 3 Latrunculin B and analogs showed antiangiogenic, antimetastatic, and antimicrobial activities.4 The most important biological effects of latrunculins are their abilities to disrupt microfilament organization and inhibit microfilament-mediated processes without affecting the organization of the microtubular system. 5 The latrunculins bind reversibly to the cytoskeleton actin monomers, forming 1:1 complexes with G-actin and disrupting polymerization. 5 Actin-active agents are attracting more attention in the field of cancer chemotherapy because microfilament and microtubule proteins form versatile dynamic polymers that can define cell polarity, organize cytoplasmic organelles, control cell shape and promote stable cell-cell and cell-matrix adhesions, and generate protrusive forces required for migration. 6-8 These functions usually fail and become abnormal in cancer cells. 6 Based on X-ray crystallography, the binding site of 1 has been located between subdomains II and IV, in the vicinity of the ATP binding cleft of the protein target in the actin monomer. 9, 10 The binding pharmacophores of 1 to G-actin were identified as follows: C-1 carbonyl oxygen through water to glutamate 214 carboxy, C-17 lactol hydroxyl to arginine 210 NH (major binding), C-17 pyran oxygen to tyrosine 69 hydroxy, thiazolidinone NH to aspartate 157 carboxy, and thiazolidinone C-20 carbonyl oxygen to threonine 186 hydroxy. 9, 10 Only the thiazolidinone NH group acts as a hydrogen bonding donor while the rest of the binding functions act as hydrogen bonding acceptors.9 , 10Semi-s...

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“…Particularly, the marine sponge is one of the best suppliers of these agents (5). 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).…”

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confidence: 99%

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

Watabe

Wada

Matsunaga

et al. 1996

Cell Struct. Funct.

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Keywords: rat fibroblast/actin polymerization/bistheonellide A/marinespongetoxin/cytokinesis ABSTRACT. Bistheonellide A, an inhibitor of actin polymerization from the marine sponge Theonella sp., was introduced at a concentration of 100 nM into rat 3Y1 fibroblast of 2.4 x 104 cells/ml. Within 1 h, it disrupted stress fibers, accompanied by a marked change of the cell morphology, resulting in the formation of processes from the cell surface. Further incubation for 24 h in the presence of 100 nMbistheonellide A led to binucleation in most cells and subsequent inhibition of cell cycle progression. Whenbistheonellide A was withdrawn from the culture medium, binuclear cells began to grow again within 20 h and reverted to mononuclear morphology. Flow cytometric analysis by fluorescence-activated cell sorting showed that 2C diploid DNAcontent in Gl phase was changed into 4C content of tetraploid for the bistheonellide A treated-cells in Gl phase and into 8C content during G2 and M phase. Therefore, we suggested that the bistheonellide A treatment inhibited cytokinesis, but not mitosis in M phase, and that treated cells were arrested at the early Gl phase. These effects of bistheonellide A on the cell cycle progression of 3Y1fibroblast were also observed more prominently in cells synchronized in S phase with hydroxyurea. Cells in GOphase were then activated by the addition of fetal calf serum in the presence of 100 nMbistheonellide A. Cell cycle progression of the bistheonellide A-treated cells was obviously slowed downor completely inhibited during Gl phase. These results reveal that actin filaments are not only essential to cytokinesis but also for promoting the progression of cell cycle from Gl to S phase. Actin, the kinetic and structural protein characterized as an inner muscle constituent, exists in all eukaryotic cells. Intracellular actin molecules form a cytoskeletal filamentous structure consisting of micro filaments. Moreover, actin filaments becomethe major component of the contractile ring in telophase and carry out cytokinesis (1). These dynamic functions of actin filaments depend on the regulation of the monomer polymerization and the filament assembly under the influence of various actin-binding proteins beside the interaction with myosin (2).

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Latrunculin, a new 2-thiazolidinone macrolide from the marine sponge

Cited by 163 publications

References 1 publication

Inhibiting diatom motility: a new tool for the study of the photophysiology of intertidal microphytobenthic biofilms

Inhibiting diatom motility: a new tool for the study of the photophysiology of intertidal microphytobenthic biofilms

Latrunculin A and Its C-17-O-Carbamates Inhibit Prostate Tumor Cell Invasion and HIF-1 Activation in Breast Tumor Cells

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

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