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
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References
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.
Bryan, J., 1972, Definition of three classes of binding sites in isolated microtubule crystals, Biochem., 11: 2611–2616.
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.
Deery, W. J. and Weisenberg, R. C., 1981, Kinetic and steady-state analysis of microtubules in the presence of colchicine, Biochem., 20: 2316–2324.
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.
Dustin, P.7 1978, “Microtubules,” Springer-Verlag, Berlin.
Farrell, K. W. and Wilson, L., 1984, The differential kinetic stabilization of opposite microtubule ends by tubulin-colchicine complexes, Biochem., 23: 3741–3748.
Garland, D. L., 1978, Kinetics and mechanism of colchicine binding to tubulin: evidence for ligand-induced conformational change, Biochem., 17: 4266–4272.
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.
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.
Kilmartin, J., 1981, Purification of yeast tubulin by self-assembly i£ vitro, Biochem., 20: 3629–3633.
Kingsbury, E. W. and Volez, H., 1969, Induction of helical arrays of ribosomes by vinblastine sulfate in Escherichia coli, Science, 166: 768–769.
Marantz, R., Ventilla, M. and Shelanski, M., 1969, Vinblastine-induced precipitation of microtubule protein, Science, 165: 498–499.
Margolis, R. L. and Wilson, L., 1981, Microtubule treadmills-possible molecular machinery, Nature (London), 293: 705–711.
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.
Na, G. C. and Timasheff, S. N., 1980a, Stoichiometry of the vinblastine-induced self-association of calf brain tubulin, Biochem., 19: 1347–1354.
Na, G. C. and Timasheff, S. N., 1980b, Thermodynamic linkage between tubulin self-association and the binding of vinblastine, Biochem., 19: 1355–1369.
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.
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.
Olmsted, J. B. and Borisy, G. G., 1973, Characterization of microtubule assembly in porcine brain extracts by viscometry, Biochem., 12: 4282–4289.
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.
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.
Wilson, L., 1975, Microtubules as drug receptors: Pharmacological properties of microtubule protein, Ann. N.Y. Acad. Sci., 253: 213-231.
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.
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.
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.
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.
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© 1986 Plenum Press, New York
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Wilson, L. (1986). Microtubules as Targets for Drug and Toxic Chemical Action: The Mechanisms of Action of Colchicine and Vinblastine. In: Clarkson, T.W., Sager, P.R., Syversen, T.L.M. (eds) The Cytoskeleton. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2161-3_3
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DOI: https://doi.org/10.1007/978-1-4613-2161-3_3
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