Disease relevance of NSC613009

• BACKGROUND: Jasplakinolide, a cyclodepsipeptide produced by an Indo-Pacific sponge, Jaspis johnstoni, has been reported to inhibit the growth of breast cancer cells [1].
• Motility of the bacterium Listeria in infected PtK2 cells was reduced 2.3-fold within 3 minutes of treatment with 1 microM jasplakinolide [2].
• Exposure of macrophages to jasplakinolide, an agent that increases actin polymerization, also impaired their ability to phagocytose Klebsiella [3].
• HA in filamentous virions and jasplakinolide-induced annuli was detergent insoluble at 4 degrees C. Furthermore, in both cases HA partitioned into low buoyant density detergent-insoluble glycolipid domains, indicating that filamentous virions and annuli contain reorganised lipid rafts [4].
• The microfilament-disrupting agent cytochalasin D protected cultured rat hippocampal neurons against glutamate toxicity, whereas the actin filament-stabilizing agent jasplakinolide potentiated glutamate toxicity [5].

High impact information on NSC613009

• GLUT4myc externalization and membrane ruffles were reduced by jasplakinolide and by swinholide-A, drugs that affect actin filament stability and prevent actin branching, respectively [6].
• We studied the effects of the chondramides (A, B, C, and D) on tumor cell growth, on cytoskeletal structure, and on actin polymerization in vitro and compared these effects with those of cytochalasin D and jasplakinolide [7].
• Concentrations that inhibited proliferation by 50% (IC50 values) ranged from 3 to 85 nM and were of the same order of magnitude as those found for cytochalasin D and jasplakinolide [7].
• The effects of jasplakinolide on the cytoskeleton were studied by fluorescent microscopy, using rhodamine phalloidin (RP) and antibodies to cytoskeletal components [1].
• The growth-inhibitory effect of jasplakinolide on the PC-3 cell line was studied in detail to elucidate its mechanism of action [1].

Biological context of NSC613009

• Actin cytoskeletal disassembly with latrunculin A enhanced insulin secretion, whereas stabilization with jasplakinolide inhibited secretion, consistent with the actin cytoskeleton serving as a barrier to exocytosis in these cells [8].
• The authors previously observed that actin stabilization by the cell permeant agent jasplakinolide enhanced cell death upon interleukin (IL)-2 or IL-3 withdrawal from growth-factor-dependent lymphocyte cell lines, and hypothesized that actin polymerization could alter the activity of gelsolin, thus enhancing apoptosis [9].
• Here the authors show that constitutive overexpression of gelsolin did not, however, inhibit or dramatically enhance apoptotic cell death upon growth-factor withdrawal, nor did it modify sensitivity to jasplakinolide [9].
• Finally, treatment with jasplakinolide, an inhibitor of actin turnover, resulted in dose-dependent inhibition of beta(2)AR internalization, suggesting that turnover of actin filaments at the receptor complex is required for endocytosis [10].
• Effects of jasplakinolide on the kinetics of actin polymerization. An explanation for certain in vivo observations [11].

Anatomical context of NSC613009

• To address the possibility that actin also participates in the transduction of an apoptotic signal, we have studied the response of the murine interleukin 2 (IL-2)-dependent T cell line CTLL-20 to treatment with the actin-binding compound jasplakinolide upon IL-2 deprivation [12].
• Expected consequences of jasplakinolide function are consistent with the experimental observations and include de novo nucleation resulting in disordered polymeric actin and in insufficient monomeric actin to allow for remodeling of stress fibers [11].
• JAS treatment caused YFP-actin to redistribute to the apical and posterior ends, where filaments formed a spiral pattern subtending the plasma membrane [13].
• Both inhibition of actin polymerization by cytochalasin D and stabilization of existing actin filaments by jasplakinolide resulted in increased Sox9 mRNA levels, whereas inhibition of microtubule polymerization by colchicine completely blocked Sox9 expression [14].
• In non-migrating chick fibroblasts, there was a delay in the onset of jasplakinolide-induced inhibition of lamellipodium protrusion, during which lamellipodium length increased linearly with no increase in protrusion rate [2].

Associations of NSC613009 with other chemical compounds

• Using the actin-stabilizing and depolymerizing drugs jasplakinolide (Jasp) and latrunculin B, we demonstrate that changes in actin filament levels or dynamics play a functional role in initiating PCD in P. rhoeas pollen, triggering a caspase-3-like activity [15].
• Interestingly, broad-spectrum inhibitors of protein tyrosine kinases (genistein) and protein tyrosine phosphatases (orthovanadate), and actin filament stabilizing compound (jasplakinolide), also block protrusive activity of the Matrigel-embedded cells but have no effect on the production of MMP-2 [16].
• Surprisingly, however, stabilization of F-actin with jasplakinolide also resulted in a dose-dependent inhibition of insulin-stimulated glucose uptake and GLUT4 translocation [17].
• The actin-stabilizing agents, phalloidin and jasplakinolide, did not modify the effects of these ahnak protein fragments on calcium current in control conditions nor in the presence of isoprenaline [18].
• The F-actin stabilizer jasplakinolide prevented both ZO-1 redistribution and albumin leakage, suggesting that actin cytoskeleton rearrangement is instrumental to podocyte permselective dysfunction induced by Ang II [19].

Gene context of NSC613009

• Agents that modulate the actin cytoskeleton (cytochalasin D and jasplakinolide) altered the plasma membrane mobility of CFTR but not CFTR- DeltaTRL [20].
• With this assay, the known actin-inhibiting drugs latrunculin-A and jasplakinolide were shown to inhibit the transition in a dose-dependent and reversible manner [21].
• The response to sulphatides was inhibited by jasplakinolide, an actin-polymerising agent known to downregulate surface expression of L-selectin, Fc gamma RIIIb, CD43 and CD44 [22].
• A functioning actin cytoskeleton was important for VCAM-1 and ICAM-1 expression as both cytochalasin D, an actin filament disruptor, and jasplakinolide, an actin filament stabilizer, attenuated the expression of these CAMs [23].
• Moreover, PAR2-like PAR1-stimulated exocytosis requires actin cytoskeleton remodeling, because vWF release is inhibited if the cells were pretreated with Jasplakinolide [24].

Analytical, diagnostic and therapeutic context of NSC613009

• Like jasplakinolide, (-)-doliculide caused the hyperassembly of purified actin into F-actin as measured both fluorometrically and by centrifugation [25].
• Although previous studies have suggested that JAS induces rigor, videomicroscopy demonstrated that JAS treatment increased the rate of parasite gliding by approximately threefold, indicating that filaments are rate limiting for motility [13].
• Jasplakinolide-induced apoptosis did not disrupt focal adhesions, whereas cytochalasin D-induced apoptosis decreased focal adhesion protein expression and occurred despite ligation of the fibronectin receptor [26].
• Furthermore, electron microscopy revealed that jasplakinolide, which stabilizes actin filaments, prevented the dispersion, but not the vesiculation of the Golgi cisternae [27].
• The stabilisation of magnesium actin filaments by phalloidin and jasplakinolide was studied using the method of differential scanning calorimetry [28].

References