Actin-Binding Drugs: An Elegant Tool to Dissect Subcellular Processes in Endothelial and Cancer Cells

  • Filip Braet
  • Lilian Soon
  • Katrien Vekemans
  • Pall Thordarson
  • Ilan Spector
Part of the Protein Reviews book series (PRON, volume 8)

Until a decade or so ago there were only a few agents available that interfered with cellular activities by binding to actin. In fact, most of our initial knowledge concerning the involvement of actin in basic cellular processes was based on the extensive use of the mold metabolites cytochalasins. However, the actin-binding activities and cellular effects of cytochalasins are complex and difficult to interpret (Cooper 1987; Sampath and Pollard 1991), so that the functions and dynamics of the actin cytoskeleton in various organisms remained elusive. Another widely used class of actin-binding drugs, the mushroom-derived phallotoxins, stabilizes actin filaments and promotes actin polymerization (Cooper 1987; Sampath and Pollard 1991), but they do not enter most cell types and are predominantly used as fluorescent derivatives to visualize actin filaments in fixed cells.


Actin Filament Actin Cytoskeleton Cell Margin Actin Organization Actin Remodel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ayscough, K. 1998. Use of latrunculin-A, an actin monomer-binding drug. Meth. Enzymol., 298, 18-25.CrossRefPubMedGoogle Scholar
  2. Braet, F. 2004. How molecular microscopy revealed new insights in the dynamics of hepatic endothelial fenestrae in the past decade. Liver Int. 24, 532-539.CrossRefPubMedGoogle Scholar
  3. Braet, F., De Zanger, R., Jans, D., Spector, I. and Wisse, E. 1996. Microfilament disrupting agent latrunculin A induces an increased number of fenestrae in rat liver sinusoidal endothelial cells: Comparison with cytochalasin B. Hepatology 24, 627-635.CrossRefPubMedGoogle Scholar
  4. Braet, F., Spector, I., De Zanger, R. and Wisse, E. 1998. A novel structure involved in the formation of liver endothelial cell fenestrae revealed using the actin inhibitor misakinolide. Proc. Natl Acad. Sci. USA 95, 13635-13640.CrossRefPubMedGoogle Scholar
  5. Braet, F., Spector, I., Shochet, N. R., Crews, P., Higa, T., Menu, E., De Zanger, R. and Wisse, E. 2002. The new anti-actin agent dihydrohalichondramide reveals fenestraeforming centers in hepatic endothelial cells. BMC Cell Biol. 3, 7.CrossRefPubMedGoogle Scholar
  6. Braet, F., Vekemans, K., Morselt, H., De Zanger, R., Wisse, E., Scherphof, G. and Kamps, J. 2004. The effect of cytochalasin B-loaded liposomes on the ultrastructure of the liver sieve. Comp. Hepatol. 3, S27.CrossRefPubMedGoogle Scholar
  7. Braet, F. and Wisse, E. 2002. Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: A review. Comp. Hepatol. 1, 1.CrossRefPubMedGoogle Scholar
  8. Braet, F., Wisse, E., Bomans, P., Frederik, P., Geerts, W., Koster, A., Soon, L. and Ringer, S. 2007. Contribution of high-resolution correlative imaging techniques in the study of the hepatic sieve in three-dimensions. Microsc. Res. Tech. 70, 230-242.CrossRefPubMedGoogle Scholar
  9. Bubb, M. R., Senderowicz, A. M., Sausville, E. A., Duncan, K. L. and Korn, E. D. 1994. Jasplakinolide, a cytotoxic natural product, induces actin polymerization and competitively inhibits the binding of phalloidin to F-actin. J. Biol. Chem. 269, 14869-14871.PubMedGoogle Scholar
  10. Bubb, M. R., Spector, I., Bershadsky, A. D. and Korn, E. D. 1995. Swinholide A is a microfilament disrupting marine toxin that stabilizes actin dimers and severs actin filaments. J. Biol. Chem. 270, 3463-3466.CrossRefPubMedGoogle Scholar
  11. Carragher, N. O. and Frame, M. C. 2004. Focal adhesion and actin dynamics: A place where kinases and proteases meet to promote invasion. Trends Cell Biol. 14, 241-249.CrossRefPubMedGoogle Scholar
  12. Cooper, J. A. 1987. Effects of cytochalasin and phalloidin on actin. J. Cell Biol. 105, 1473-1478.CrossRefPubMedGoogle Scholar
  13. Coue, M., Brenner, S. L., Spector, I. and Korn, E. D. 1987. Inhibition of actin polymerization by latrunculin A. FEBS Lett. 213, 316-318.CrossRefPubMedGoogle Scholar
  14. Eash, S., and Atwood, W. J. 2005. Involvement of cytoskeletal components in BK virus infectious entry. J. Virol. 79, 11734-11741.CrossRefPubMedGoogle Scholar
  15. Fenteany, G. and Zhu, S. 2003. Small-molecule inhibitors of actin dynamics and cell motility. Curr. Top. Med. Chem. 3, 593-616.CrossRefPubMedGoogle Scholar
  16. Fraser, R., Dobbs, B. R. and Rogers, G. W. T. 1995. Lipoproteins and the liver sieve: The role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis. Hepatology 21, 863-874.PubMedGoogle Scholar
  17. Giganti, A. and Friederich, E. 2003. The actin cytoskeleton as a therapeutic target: State of the art and future directions. Prog. Cell Cycle Res. 5, 511-525.PubMedGoogle Scholar
  18. Gourlay, C. W. and Ayscough, K. R. 2005. The actin cytoskeleton: A key regulator of apoptosis and ageing? Nat. Rev. Mol. Cell Biol. 6, 583-589.CrossRefPubMedGoogle Scholar
  19. Hayot, C., Debeir, O., Van Ham, P., Van Damme, M., Kiss, R. and Decaestecker, C. 2006. Characterization of the activities of actin-affecting drugs on tumor cell migration. Toxicol. Appl. Pharmacol. 211, 30-40.CrossRefPubMedGoogle Scholar
  20. Johnson, D. H. 1997. The effect of cytochalasin D on outflow facility and the trabecular meshwork of the human eye in perfusion organ culture. Invest. Ophthalmol. Vis. Sci. 38, 2790-2799.PubMedGoogle Scholar
  21. Kim, R. 2005. Recent advances in understanding the cell death pathways activated by anticancer therapy. Cancer 103, 1551-1560.CrossRefPubMedGoogle Scholar
  22. Koning, G. A., Morselt, H. W. M., Gorter, A., Allen, T. M., Zalipsky, S., Scherphof, G. L. and Kamps, J. A. A. M. 2003. Interaction of differently designed immunoliposomes with colon cancer cells and Kupffer cells: An in vitro comparison. Pharm. Res. 20, 1249-1257.CrossRefPubMedGoogle Scholar
  23. Lambrechts, A., Van Troys, M. and Ampe, C. 2004. The actin cytoskeleton in normal and pathological cell motility. Int. J. Biochem. Cell Biol. 36, 1890-1909.CrossRefPubMedGoogle Scholar
  24. Lievens, J., Snoeys, J., Vekemans, K., Van Linthout, S., De Zanger, R., Collen, D., Wisse, E. and De Geest, B. 2004. The size of sinusoidal fenestrae is a critical determinant of hepatocyte transduction after adenoviral gene transfer. Gene Ther. 11, 1523-1531.CrossRefPubMedGoogle Scholar
  25. Okka, M., Tian, B. and Kaufman, P. L. 2004. Effect of low-dose latrunculin B on anterior segment physiologic features in the monkey eye. Arch. Ophthalmol. 122, 482-488.CrossRefGoogle Scholar
  26. Peterson, J. A., Tian, B., Geiger, B. and Kaufman, P. L. 1999. Latrunculin-A causes mydriasis and cycloplegia in the cynomolgus monkey. Invest. Ophthalmol. Vis. Sci. 40,631-938.PubMedGoogle Scholar
  27. Posey, S. C., Bierer, B. E. 1999. Actin stabilization by jasplakinolide enhances apoptosis induced by cytokine deprivation. J. Biol. Chem. 274, 4259-4265.CrossRefPubMedGoogle Scholar
  28. Rao, J. and Li, N. 2004. Microfilament actin remodeling as a potential target for cancer drug development. Curr. Cancer Drug Targets 44, 345-354.CrossRefGoogle Scholar
  29. Richardso, P., Kren, B. T. and Steer, C. J. 2002. In vivo application of non-viral vectors to the liver. J. Drug Target, 10, 123-131.CrossRefPubMedGoogle Scholar
  30. Salu, K. J., Huang, Y., Bosmans, J. M., Liu, X., Li, S., Wang, L., Verbeken, E., Bult, H., Vrints, C. J. and De Scheerder, I. K. 2003. Addition of cytochalasin D to a biocompatible oil stent coating inhibits intimal hyperplasia in a porcine coronary model. Coron. Artery Dis. 14, 545-555.CrossRefPubMedGoogle Scholar
  31. Sampath, P. and Pollard, T. D. 1991. Effects of cytochalasin, phalloidin, and pH on the elongation of actin filaments. Biochemistry 30, 1973-1980.CrossRefPubMedGoogle Scholar
  32. Senderowicz, A. M., Kaur, G., Sainz, E., Laing, C., Inman, W. D., Rodriguez, J., Crews, P., Malspeis, L., Grever, M. R., Sausville, E. A. and Duncan, L. K. 1995. Jasplakinolide’s inhibition of the growth of prostate carcinoma cells in vitro with disruption of the actin cytoskeleton. J. Natl Cancer Inst. 87, 46-51.CrossRefPubMedGoogle Scholar
  33. Spector, I., Braet, F., Shochet, N. R. and Bubb, M. R. 1999. New anti-actin drugs in the study of the organization and function of the actin cytoskeleton. Microsc. Res. Tech. 47, 18-37.CrossRefPubMedGoogle Scholar
  34. Spector, I., Shochet, N. R., Blasberger, D. and Kashman, Y. 1989. Latrunculins: Novel marine macrolides that disrupt microfilament organization and affect cell growth: I. Comparison with cytochalasin D. Cell Motil. Cytoskel. 13, 127-144.CrossRefGoogle Scholar
  35. Spector, I., Shochet, N. R., Kashman, Y. and Groweiss, A. 1983. Latrunculins: Novel marine toxins that disrupt microfilament organization in cultured cells. Science 219, 493-495.CrossRefPubMedGoogle Scholar
  36. Steffan, A. M., Gendrault, J. L., Kirn, A. 1987. Increase in the number of fenestrae in mouse endothelial liver cells by altering the cytoskeleton with cytochalasin B. Hepatology 7, 1230-1238.CrossRefPubMedGoogle Scholar
  37. Stingl, J., Andersen, R. J. and Emerman, J. T. 1992. In vitro screening of crude extracts and pure metabolites obtained from marine invertebrates for the treatment of breast cancer. Cancer Chemother. Pharmacol. 30, 401-406.Google Scholar
  38. Takeuchi, H., Ara, G., Sausville, E. A. and Teicher, B. 1998. Jasplakinolide: Interaction with radiation and hyperthermia in human prostate carcinoma and Lewis lung carcinoma. Cancer Chemother. Pharmacol. 42, 491-496.Google Scholar
  39. Terry, D. R., Spector, I., Higa, T. and Bubb, M. R. 1997. Misakinolide A is a marine macrolide that caps but does not sever filamentous actin. J. Biol. Chem. 272, 7841-7845.CrossRefPubMedGoogle Scholar
  40. Tian, B., Kiland, J. A. and Kaufman, P. L. 2001. Effects of the marine macrolides swinholide A and jasplakinolide on outflow facility in monkeys. Invest. Ophthalmol. Vis. Sci. 42, 3187-3192.PubMedGoogle Scholar
  41. Vázquez-López, A., Sierra-Paredes, G. and Sierra-Marcuno, G. 2005. Seizures induced by microperfusion of glutamate and glycine in the hippocampus of rats pretreated with latrunculin A. Neurosci. Lett. 388, 81-85.CrossRefPubMedGoogle Scholar
  42. Yeung, K. S. and Paterson, I. 2002. Actin-binding marine macrolides: Total synthesis and biological importance. Angew. Chem. Int. Ed. Engl. 41, 4632-4653.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Filip Braet
    • 1
  • Lilian Soon
    • 1
  • Katrien Vekemans
    • 2
  • Pall Thordarson
    • 3
  • Ilan Spector
    • 4
  1. 1.Australian Key Centre for Microscopy and Microanalysis (AKCMM), Electron Microscope UnitThe University of SydneyAustralia
  2. 2.Abdominal Transplant Surgery, Department of SurgeryCatholic University of LeuvenLeuvenBelgium
  3. 3.School of ChemistryThe University of SydneySydneyAustralia
  4. 4.Department of Physiology and Biophysics, Health Science CenterState University of New York at Stony Brook (SUNY), Stony BrookNew YorkUSA

Personalised recommendations