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Chemical Compound Review

jasplakinolide     (7R,10S,13S,15E,17R,19S)-7- [(2-bromo-1H...

Synonyms: NSC613009, AC1NS0C9
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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


Analytical, diagnostic and therapeutic context of NSC613009


  1. Jasplakinolide's inhibition of the growth of prostate carcinoma cells in vitro with disruption of the actin cytoskeleton. Senderowicz, A.M., Kaur, G., Sainz, E., Laing, C., Inman, W.D., Rodríguez, J., Crews, P., Malspeis, L., Grever, M.R., Sausville, E.A. J. Natl. Cancer Inst. (1995) [Pubmed]
  2. Role of actin-filament disassembly in lamellipodium protrusion in motile cells revealed using the drug jasplakinolide. Cramer, L.P. Curr. Biol. (1999) [Pubmed]
  3. Hyperoxia impairs antibacterial function of macrophages through effects on actin. O'Reilly, P.J., Hickman-Davis, J.M., Davis, I.C., Matalon, S. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  4. A functional link between the actin cytoskeleton and lipid rafts during budding of filamentous influenza virions. Simpson-Holley, M., Ellis, D., Fisher, D., Elton, D., McCauley, J., Digard, P. Virology (2002) [Pubmed]
  5. Evidence that actin depolymerization protects hippocampal neurons against excitotoxicity by stabilizing [Ca2+]i. Furukawa, K., Smith-Swintosky, V.L., Mattson, M.P. Exp. Neurol. (1995) [Pubmed]
  6. Insulin-induced cortical actin remodeling promotes GLUT4 insertion at muscle cell membrane ruffles. Tong, P., Khayat, Z.A., Huang, C., Patel, N., Ueyama, A., Klip, A. J. Clin. Invest. (2001) [Pubmed]
  7. The chondramides: cytostatic agents from myxobacteria acting on the actin cytoskeleton. Sasse, F., Kunze, B., Gronewold, T.M., Reichenbach, H. J. Natl. Cancer Inst. (1998) [Pubmed]
  8. ADP-ribosylation factor 6 regulates insulin secretion through plasma membrane phosphatidylinositol 4,5-bisphosphate. Lawrence, J.T., Birnbaum, M.J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Failure of gelsolin overexpression to regulate lymphocyte apoptosis. Posey, S.C., Martelli, M.P., Azuma, T., Kwiatkowski, D.J., Bierer, B.E. Blood (2000) [Pubmed]
  10. Agonist-stimulated beta-adrenergic receptor internalization requires dynamic cytoskeletal actin turnover. Volovyk, Z.M., Wolf, M.J., Prasad, S.V., Rockman, H.A. J. Biol. Chem. (2006) [Pubmed]
  11. Effects of jasplakinolide on the kinetics of actin polymerization. An explanation for certain in vivo observations. Bubb, M.R., Spector, I., Beyer, B.B., Fosen, K.M. J. Biol. Chem. (2000) [Pubmed]
  12. Actin stabilization by jasplakinolide enhances apoptosis induced by cytokine deprivation. Posey, S.C., Bierer, B.E. J. Biol. Chem. (1999) [Pubmed]
  13. Actin filament polymerization regulates gliding motility by apicomplexan parasites. Wetzel, D.M., Håkansson, S., Hu, K., Roos, D., Sibley, L.D. Mol. Biol. Cell (2003) [Pubmed]
  14. RhoA/ROCK signaling regulates Sox9 expression and actin organization during chondrogenesis. Woods, A., Wang, G., Beier, F. J. Biol. Chem. (2005) [Pubmed]
  15. Actin depolymerization is sufficient to induce programmed cell death in self-incompatible pollen. Thomas, S.G., Huang, S., Li, S., Staiger, C.J., Franklin-Tong, V.E. J. Cell Biol. (2006) [Pubmed]
  16. Function of alpha3beta1-tetraspanin protein complexes in tumor cell invasion. Evidence for the role of the complexes in production of matrix metalloproteinase 2 (MMP-2). Sugiura, T., Berditchevski, F. J. Cell Biol. (1999) [Pubmed]
  17. Insulin-stimulated GLUT4 translocation in adipocytes is dependent upon cortical actin remodeling. Kanzaki, M., Pessin, J.E. J. Biol. Chem. (2001) [Pubmed]
  18. Calcium current in rat cardiomyocytes is modulated by the carboxyl-terminal ahnak domain. Alvarez, J., Hamplova, J., Hohaus, A., Morano, I., Haase, H., Vassort, G. J. Biol. Chem. (2004) [Pubmed]
  19. Permselective dysfunction of podocyte-podocyte contact upon angiotensin II unravels the molecular target for renoprotective intervention. Macconi, D., Abbate, M., Morigi, M., Angioletti, S., Mister, M., Buelli, S., Bonomelli, M., Mundel, P., Endlich, K., Remuzzi, A., Remuzzi, G. Am. J. Pathol. (2006) [Pubmed]
  20. Increased diffusional mobility of CFTR at the plasma membrane after deletion of its C-terminal PDZ binding motif. Haggie, P.M., Stanton, B.A., Verkman, A.S. J. Biol. Chem. (2004) [Pubmed]
  21. Small-molecule inhibitors of the budded-to-hyphal-form transition in the pathogenic yeast Candida albicans. Toenjes, K.A., Munsee, S.M., Ibrahim, A.S., Jeffrey, R., Edwards, J.E., Johnson, D.I. Antimicrob. Agents Chemother. (2005) [Pubmed]
  22. Activation of NF-kappa B transcription factor in human neutrophils by sulphatides and L-selectin cross-linking. Turutin, D.V., Kubareva, E.A., Pushkareva, M.A., Ullrich, V., Sud'ina, G.F. FEBS Lett. (2003) [Pubmed]
  23. The role of the cytoskeleton in cellular adhesion molecule expression in tumor necrosis factor-stimulated endothelial cells. VandenBerg, E., Reid, M.D., Edwards, J.D., Davis, H.W. J. Cell. Biochem. (2004) [Pubmed]
  24. Differential actions of PAR2 and PAR1 in stimulating human endothelial cell exocytosis and permeability: the role of Rho-GTPases. Klarenbach, S.W., Chipiuk, A., Nelson, R.C., Hollenberg, M.D., Murray, A.G. Circ. Res. (2003) [Pubmed]
  25. (-)-Doliculide, a new macrocyclic depsipeptide enhancer of actin assembly. Bai, R., Covell, D.G., Liu, C., Ghosh, A.K., Hamel, E. J. Biol. Chem. (2002) [Pubmed]
  26. Initiation of apoptosis by actin cytoskeletal derangement in human airway epithelial cells. White, S.R., Williams, P., Wojcik, K.R., Sun, S., Hiemstra, P.S., Rabe, K.F., Dorscheid, D.R. Am. J. Respir. Cell Mol. Biol. (2001) [Pubmed]
  27. Cholesterol loading induces a block in the exit of VSVG from the TGN. Ying, M., Grimmer, S., Iversen, T.G., Van Deurs, B., Sandvig, K. Traffic (2003) [Pubmed]
  28. A simple model for the cooperative stabilisation of actin filaments by phalloidin and jasplakinolide. Visegrády, B., Lorinczy, D., Hild, G., Somogyi, B., Nyitrai, M. FEBS Lett. (2005) [Pubmed]
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