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Microtubules as Targets for Drug and Toxic Chemical Action: The Mechanisms of Action of Colchicine and Vinblastine

  • Leslie Wilson

Abstract

Colchicine (Fig. 1), the earliest chemical substance discovered that acts on microtubules, was initially described as a spindle poison in the 1930s because it produced strikingly disorganized mitotic spindles and chromosome patterns in treated cells (reviewed by Dustin, 1978). It was many years before it was established that the mechanism of action of colchicine involved disruption of microtubules (see Borisy and Taylor, 1967a,b; Wilson and Friedkin, 1967). Other microtubule-disruptive substances originally identified as spindle poisons include griseofulvin (see Deysson, 1964), podophyllotoxin, a plant alkaloid that binds to tubulin in the vicinity of the colchicine binding site (see Wilson, 1975), and a clinically important group of alkaloids commonly known as the “vinca alkaloids.” These drugs were discovered in 1957 in extracts of the plant Catharanthus rosea, originally called Vinca rosea (Cutts et al., 1957; Noble et al., 1958). Three vinca alkaloids, vinblastine, vincristine (Fig. 1), and vindesine, are currently used for the treatment of several forms of cancer (Gerzon, 1980).

Keywords

Vinca Alkaloid Microtubule Assembly Dissociation Rate Constant High Affinity Binding Site Microtubule Protein 
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.

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References

  1. Bonhaus, D. W., McTormack, K. M., Mayor, G. H., Mattson, J.C. and Hook, J.B., 1980, The effects of aluminum on microtubular integrity using in vitro and in vivo models, Toxicol.Let., 6: 141–147.Google Scholar
  2. Bryan, J., 1972, Definition of three classes of binding sites in isolated microtubule crystals, Biochem., 11: 2611–2616.Google Scholar
  3. Bryan, J., Nagle, B. W. and Meza, I., 1975, Inhibition of tubulin assembly by RNA and other polyanions. A mechanism, in: “Microtubules and Microtubule Inhibitors,” M. Borgers and MT de Brabander, eds., pp. 91–101, North-Holland, Amsterdam.Google Scholar
  4. Deery, W. J. and Weisenberg, R. C., 1981, Kinetic and steady-state analysis of microtubules in the presence of colchicine, Biochem., 20: 2316–2324.Google Scholar
  5. Detrich, H. W., III, Williams, R. C., Jr., MacDonald, T. L., Wilson, L. and Puett, D., 1981, Changes in the circular dichroic spectrum of colchicine associated with its binding to tubulin, Biochem., 20: 5999–6005.Google Scholar
  6. Dustin, P.7 1978, “Microtubules,” Springer-Verlag, Berlin.Google Scholar
  7. Farrell, K. W. and Wilson, L., 1984, The differential kinetic stabilization of opposite microtubule ends by tubulin-colchicine complexes, Biochem., 23: 3741–3748.Google Scholar
  8. Garland, D. L., 1978, Kinetics and mechanism of colchicine binding to tubulin: evidence for ligand-induced conformational change, Biochem., 17: 4266–4272.Google Scholar
  9. Gerzon, K., 1980, Dimeric catharanthus alkaloids, in; “Anticancer Agents Based on Natural Product Models,” J. M. Cassaday and J.D. Douros, eds., pp. 271–317, Academic Press, New York.Google Scholar
  10. Himes, R. H., Kersey, R. N., Heller-Bettinger, I. and Samson, F. E., 1976, Action of the Vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro, Cancer Res., 36: 3798–3802.Google Scholar
  11. Kilmartin, J., 1981, Purification of yeast tubulin by self-assembly i£ vitro, Biochem., 20: 3629–3633.Google Scholar
  12. Kingsbury, E. W. and Volez, H., 1969, Induction of helical arrays of ribosomes by vinblastine sulfate in Escherichia coli, Science, 166: 768–769.Google Scholar
  13. Marantz, R., Ventilla, M. and Shelanski, M., 1969, Vinblastine-induced precipitation of microtubule protein, Science, 165: 498–499.Google Scholar
  14. Margolis, R. L. and Wilson, L., 1981, Microtubule treadmills-possible molecular machinery, Nature (London), 293: 705–711.Google Scholar
  15. Margolis, R. L., Rauch, C. T. and Wilson, L., 1980, Mechanism of colchicine-dimer addition to microtubule ends: Implications for the microtubule polymerization mechanism, Biochemistry, 19: 5550–5557.Google Scholar
  16. Na, G. C. and Timasheff, S. N., 1980a, Stoichiometry of the vinblastine-induced self-association of calf brain tubulin, Biochem., 19: 1347–1354.Google Scholar
  17. Na, G. C. and Timasheff, S. N., 1980b, Thermodynamic linkage between tubulin self-association and the binding of vinblastine, Biochem., 19: 1355–1369.Google Scholar
  18. Noble, R. L., Beer, C. T. and Cutts, J. H., 1958, Role of chance observations in chemotherapy: Vinca rosea, Ann. N.Y. Acad. Sci., 76: 882–894.CrossRefGoogle Scholar
  19. O’Brien, E. T., Jacobs, R. S. and Wilson, L., 1983, Inhibition of bovine brain microtubule assembly in vitro by stypoldione, MoT. Pharmacol., 24: 493-499.Google Scholar
  20. Olmsted, J. B. and Borisy, G. G., 1973, Characterization of microtubule assembly in porcine brain extracts by viscometry, Biochem., 12: 4282–4289.Google Scholar
  21. Remillard, S., Rebhun, L. I., Howie, G. A. and Kupchan, S. M., 1975, Antimitotic activity of the potent tumor inhibitor maytansine, Science, 189: 1002–1005.Google Scholar
  22. Schochet, S. S., Jr., Lambert, P. W. and Earle, K. M., 1968, Neuronal changes induced by intrathecal vincristine sulfate, J. Neuropathol. Exp. Neurol., 27:645–658. Sternlicht, H. and Ringel, I., 1979, Colchicine inhibition of microtubule assembly via copolymer formation, J. Biol. Chem., 254: 10540-10550.Google Scholar
  23. Wilson, L., 1975, Microtubules as drug receptors: Pharmacological properties of microtubule protein, Ann. N.Y. Acad. Sci., 253: 213-231.Google Scholar
  24. Wilson, L. and Friedkin, M., 1967, The biochemical events of mitosis. II. The in vivo and in vitro binding of colchicine in grasshopper embryos and Tts possible relation to inhibition of mitosis, Biochem., 6: 3126-3135.Google Scholar
  25. Wilson, L. and Meza, I., 1973, The mechanism of action of colchicine. Colchicine binding properties of sea urchin sperm tail outer doublet tubulin, J. Cell Biol., 58: 709-719.Google Scholar
  26. Wilson, L., Bryan, J., Ruby, A. and Mazia, D., 1970, Precipitation of proteins by vinblastine and calcium ions, Proc. Nat. Acad. Sci., 66: 807-814.Google Scholar
  27. Wilson, L., Snyder, K. B., Thompson, W. C. and Margolis, R. L., 1982a, A rapid filtration assay for analysis of microtubule assembly, disassembly and steady-state tubulin, Methods in Cell Biol., 24: 159–169.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Leslie Wilson
    • 1
  1. 1.Department of Biological SciencesUniversity of CaliforniaSanta BarbaraUSA

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