Skip to main content
Log in

Microtubule drugs: action, selectivity, and resistance across the kingdoms of life

  • Review Article
  • Published:
Protoplasma Aims and scope Submit manuscript

Abstract

Microtubule drugs such as paclitaxel, colchicine, vinblastine, trifluralin, or oryzalin form a chemically diverse group that has been reinforced by a large number of novel compounds over time. They all share the ability to change microtubule properties. The profound effects of disrupted microtubule systems on cell physiology can be used in research as well as anticancer treatment and agricultural weed control. The activity of microtubule drugs generally depends on their binding to α- and β-tubulin subunits. The microtubule drugs are often effective only in certain taxonomic groups, while other organisms remain resistant. Available information on the molecular basis of this selectivity is summarized. In addition to reviewing published data, we performed sequence data mining, searching for kingdom-specific signatures in plant, animal, fungal, and protozoan tubulin sequences. Our findings clearly correlate with known microtubule drug resistance determinants and add more amino acid positions with a putative effect on drug-tubulin interaction. The issue of microtubule network properties in plant cells producing microtubule drugs is also addressed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Adl SM, Simpson AGB, Farmer MA, Andersen RA, Anderson OR, Barta JR, Bowser SS et al (2005) The new higher level classification of eukaryotes with emphasis on the taxonomy of protists. J Eukaryot Microbiol 52(5):399–451. doi:10.1111/j.1550-7408.2005.00053.x

    PubMed  Google Scholar 

  • Akbari V, Moghim S, Reza Mofid M (2011) Comparison of epothilone and taxol binding in yeast tubulin using molecular modeling. Avicenna J Med Biotechnol 3(4):167–175

    CAS  PubMed Central  PubMed  Google Scholar 

  • Altland JE, Gilliam CH, Wehtje G (2003) Weed control in field nurseries. HortTechnology 13(1):9–14

    CAS  Google Scholar 

  • Amos LA (2011) What tubulin drugs tell us about microtubule structure and dynamics. Semin Cell Dev Biol 22(9):916–926. doi:10.1016/j.semcdb.2011.09.014

    CAS  PubMed  Google Scholar 

  • Anthony RG, Waldin TR, Ray JA, Bright SWJ, Hussey PJ (1998) Herbicide resistance caused by spontaneous mutation of the cytoskeletal protein tubulin. Nature 393(6682):260–263

    CAS  PubMed  Google Scholar 

  • Ascough GD, van Staden J, Erwin JE (2008) Effectiveness of colchicine and oryzalin at inducing polyploidy in Watsonia lepida N.E. Brown. HortSci 43(7):2248–2251

    Google Scholar 

  • Bai RL, Paull KD, Herald CL, Malspeis L, Pettit GR, Hamel E (1991) Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. J Biol Chem 266(24):15882–15889

    CAS  PubMed  Google Scholar 

  • Bajer AS, Molè-Bajer J (1986) Drugs with colchicine-like effects that specifically disassemble plant but not animal microtubules. Ann N Y Acad Sci 466:767–784

    CAS  PubMed  Google Scholar 

  • Baldauf SL, Palmer JD (1993) Animals and fungi are each other’s closest relatives: congruent evidence from multiple proteins. Proc Natl Acad Sci U S A 90(24):11558–11562

    CAS  PubMed Central  PubMed  Google Scholar 

  • Banerjee M, Roy D, Bhattacharyya B, Basu G (2007) Differential colchicine-binding across eukaryotic families: the role of highly conserved Pro268beta and Ala248beta residues in animal tubulin. FEBS Lett 581(26):5019–5023. doi:10.1016/j.febslet.2007.09.047

    CAS  PubMed  Google Scholar 

  • Baum SG, Wittner M, Nadler JP, Horwitz SB, Dennis JE, Schiff PB, Tanowitz HB (1981) Taxol, a microtubule stabilizing agent, blocks the replication of Trypanosoma cruzi. Proc Natl Acad Sci U S A 78(7):4571–4575

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berger CA, Witkus ER (1943) A cytological study of c-mitosis in the polysomatic plant Spinacia oleracea, with comparative observations on Allium cepa. Bull Torrey Bot Club 70(5):457. doi:10.2307/2481391

    Google Scholar 

  • Binder LI, Dentler WL, Rosenbaum JL (1975) Assembly of chick brain tubulin onto flagellar microtubules from Chlamydomonas and sea urchin sperm. Proc Natl Acad Sci U S A 72(3):1122–1126

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blakeslee AF (1939) The present and potential service of chemistry to plant breeding. Am J Bot 26(3):163. doi:10.2307/2436533

    CAS  Google Scholar 

  • Bode CJ, Gupta ML Jr, Reiff EA, Suprenant KA, Georg GI, Himes RH (2002) Epothilone and paclitaxel: unexpected differences in promoting the assembly and stabilization of yeast microtubules. Biochemistry (Mosc) 41(12):3870–3874

    CAS  Google Scholar 

  • Bollag DM, McQueney PA, Zhu J, Hensens O, Koupal L, Liesch J, Goetz M et al (1995) Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 55(11):2325–2333

    CAS  PubMed  Google Scholar 

  • Breviario D, Gianì S, Morello L (2013) Multiple tubulins: evolutionary aspects and biological implications. Plant J Cell Mol Biol 75(2):202–218. doi:10.1111/tpj.12243

    CAS  Google Scholar 

  • Brown RC, Lemmon BE (2007) The pleiomorphic plant MTOC: an evolutionary perspective. J Integr Plant Biol 49(8):1142–1153. doi:10.1111/j.1672-9072.2007.00538.x

    Google Scholar 

  • Burns RG (1992) Analysis of the colchicine-binding site of β-tubulin. FEBS Lett 297(3):205–208. doi:10.1016/0014-5793(92)80538-R

    CAS  PubMed  Google Scholar 

  • Caperta AD, Delgado M, Ressurreicao F, Meister A, Jones RN, Ressurreição F, Viegas W et al (2006) Colchicine-induced polyploidization depends on tubulin polymerization in c-metaphase cells. Protoplasma 227(2–4):147–153. doi:10.1007/s00709-005-0137-z

    CAS  PubMed  Google Scholar 

  • Cavalier-Smith T (2010) Kingdoms Protozoa and Chromista and the eozoan root of the eukaryotic tree. Biol Lett 6(3):342–345. doi:10.1098/rsbl.2009.0948

    PubMed Central  PubMed  Google Scholar 

  • Choi H-K, Kim S-I, Song J-Y, Son J-S, Hong S-S, Durzan DJ, Lee HJ (2001) Localization of paclitaxel in suspension culture of Taxus chinensis. J Microbiol Biotechnol 11(3):458–462

    CAS  Google Scholar 

  • Chrétien D, Metoz F, Verde F, Karsenti E, Wade RH (1992) Lattice defects in microtubules: protofilament numbers vary within individual microtubules. J Cell Biol 117(5):1031–1040

    PubMed  Google Scholar 

  • Correia JJ, Lobert S (2001) Physiochemical aspects of tubulin-interacting antimitotic drugs. Curr Pharm Des 7(13):1213–1228

    CAS  PubMed  Google Scholar 

  • Corson F, Hamant O, Bohn S, Traas J, Boudaoud A, Couder Y (2009) Turning a plant tissue into a living cell froth through isotropic growth. Proc Natl Acad Sci 106(21):8453–8458. doi:10.1073/pnas.0812493106

    CAS  PubMed Central  PubMed  Google Scholar 

  • Crooks GE, Hon G, Chandonia J-M, Brenner SE (2004) WebLogo: a sequence logo generator. Genome Res 14(6):1188–1190. doi:10.1101/gr.849004

    CAS  PubMed Central  PubMed  Google Scholar 

  • Das L, Bhattacharya B, Basu G (2012) Rationalization of paclitaxel insensitivity of yeast β-tubulin and human βIII-tubulin isotype using principal component analysis. BMC Res Notes 5(1):395. doi:10.1186/1756-0500-5-395

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dayan FE, Kuhajek JM, Canel C, Watson SB, Moraes RM (2003) Podophyllum peltatum possesses a beta-glucosidase with high substrate specificity for the aryltetralin lignan podophyllotoxin. Biochim Biophys Acta 1646(1–2):157–163

    CAS  PubMed  Google Scholar 

  • Degraeve N, Gilot-Delhalle J (1972) Cytological effects of vinblastine in plants. Experientia 28(5):581–582. doi:10.1007/BF01931891

    CAS  PubMed  Google Scholar 

  • Délye C, Menchari Y, Michel S, Darmency H (2004) Molecular bases for sensitivity to tubulin-binding herbicides in green foxtail. Plant Physiol 136(4):3920–3932. doi:10.1104/pp. 103.037432

    PubMed Central  PubMed  Google Scholar 

  • Dempsey E, Prudêncio M, Fennell BJ, Gomes-Santos CS, Barlow JW, Bell A (2013) Antimitotic herbicides bind to an unidentified site on malarial parasite tubulin and block development of liver-stage Plasmodium parasites. Mol Biochem Parasitol 188(2):116–127. doi:10.1016/j.molbiopara.2013.03.001

    CAS  PubMed  Google Scholar 

  • Dhamodharan R, Jordan MA, Thrower D, Wilson L, Wadsworth P (1995) Vinblastine suppresses dynamics of individual microtubules in living interphase cells. Mol Biol Cell 6(9):1215–1229

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dow GS, Armson A, Boddy MR, Itenge T, McCarthy D, Parkin JE, Thompson RCA et al (2002) Plasmodium: assessment of the antimalarial potential of trifluralin and related compounds using a rat model of malaria, Rattus norvegicus. Exp Parasitol 100(3):155–160. doi:10.1016/S0014-4894(02)00016-4

    CAS  PubMed  Google Scholar 

  • Downing KH, Nogales E (1998a) Tubulin and microtubule structure. Curr Opin Cell Biol 10(1):16–22

    CAS  PubMed  Google Scholar 

  • Downing KH, Nogales E (1998b) Tubulin structure: insights into microtubule properties and functions. Curr Opin Struct Biol 8(6):785–791

    CAS  PubMed  Google Scholar 

  • Dumontet C, Jordan MA (2010) Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 9(10):790–803. doi:10.1038/nrd3253

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fennell BJ, Naughton JA, Dempsey E, Bell A (2006) Cellular and molecular actions of dinitroaniline and phosphorothioamidate herbicides on Plasmodium falciparum: tubulin as a specific antimalarial target. Mol Biochem Parasitol 145(2):226–238. doi:10.1016/j.molbiopara.2005.08.020

    CAS  PubMed  Google Scholar 

  • Ferlini C, Cicchillitti L, Raspaglio G, Bartollino S, Cimitan S, Bertucci C, Mozzetti S et al (2009) Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res 69(17):6906–6914. doi:10.1158/0008-5472.CAN-09-0540

    CAS  PubMed  Google Scholar 

  • Feutz E (1992) Evaluating the effects of oryzalin on the germination, emergence, and vegetative vigor of non-target terrestrial plants: Lab Project Number: 40292; ABC Labs, Inc. 155 p.; MRID# 42602401. http://www.epa.gov/oppsrrd1/REDs/0186.pdf. Accessed 10 Jan 2014

  • Filho SA, Pereira de Almeida ER, Gander ES (1978) The influence of hydroxyurea and colchicine on growth and morphology of Trypanosoma cruzi. Acta Trop 35(3):229–237

    CAS  PubMed  Google Scholar 

  • Finkelstein Y, Aks SE, Hutson JR, Juurlink DN, Nguyen P, Dubnov-Raz G, Pollak U et al (2010) Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol Phila Pa 48(5):407–414. doi:10.3109/15563650.2010.495348

    CAS  Google Scholar 

  • Fojo AT, Menefee M (2005) Microtubule targeting agents: basic mechanisms of multidrug resistance (MDR). Semin Oncol 32:3–8. doi:10.1053/j.seminoncol.2005.09.010

    Google Scholar 

  • Foland TB, Dentler WL, Suprenant KA, Gupta ML Jr, Himes RH (2005) Paclitaxel-induced microtubule stabilization causes mitotic block and apoptotic-like cell death in a paclitaxel-sensitive strain of Saccharomyces cerevisiae. Yeast Chichester Engl 22(12):971–978. doi:10.1002/yea.1284

    CAS  Google Scholar 

  • Ganguly A, Cabral F (2011) New insights into mechanisms of resistance to microtubule inhibitors. Biochim Biophys Acta 1816(2):164–171. doi:10.1016/j.bbcan.2011.06.001

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ganguly A, Yang H, Cabral F (2010) Paclitaxel dependent cell lines reveal a novel drug activity. Mol Cancer Ther 9(11):2914–2923. doi:10.1158/1535-7163.MCT-10-0552

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gigant B, Ravelli R, Wang C, Knossow M, Roussi F, Steinmetz MO, Curmi PA et al (2005) Structural basis for the regulation of tubulin by vinblastine. Nature 435(7041):519–522. doi:10.1038/nature03566

    CAS  PubMed  Google Scholar 

  • Goodin S, Kane MP, Rubin EH (2004) Epothilones: mechanism of action and biologic activity. J Clin Oncol 22(10):2015–2025. doi:10.1200/JCO.2004.12.001

    CAS  PubMed  Google Scholar 

  • Grellier P, Sinou V, Garreau-de Loubresse N, Bylèn E, Boulard Y, Schrével J (1999) Selective and reversible effects of vinca alkaloids on Trypanosoma cruzi epimastigote forms: blockage of cytokinesis without inhibition of the organelle duplication. Cell Motil Cytoskeleton 42(1):36–47. doi:10.1002/(SICI)1097-0169(1999)42:1<36::AID-CM4>3.0.CO;2-G

    CAS  PubMed  Google Scholar 

  • Gull K (2001) Protist tubulins: new arrivals, evolutionary relationships and insights to cytoskeletal function. Curr Opin Microbiol 4(4):427–432. doi:10.1016/S1369-5274(00)00230-7

    CAS  PubMed  Google Scholar 

  • Gunasekera SP, Gunasekera M, Longley RE, Schulte GK (1990) Discodermolide: a new bioactive polyhydroxylated lactone from the marine sponge Discodermia dissoluta. J Org Chem 55(16):4912–4915. doi:10.1021/jo00303a029

    CAS  Google Scholar 

  • Gunning BES, Hardham AR (1982) Microtubules. Annu Rev Plant Physiol 33(1):651–698. doi:10.1146/annurev.pp. 33.060182.003251

    CAS  Google Scholar 

  • Gupta ML Jr, Bode CJ, Georg GI, Himes RH (2003) Understanding tubulin–Taxol interactions: mutations that impart Taxol binding to yeast tubulin. Proc Natl Acad Sci U S A 100(11):6394–6397. doi:10.1073/pnas.1131967100

    CAS  PubMed Central  PubMed  Google Scholar 

  • Haber JE, Peloquin JG, Halvorson HO, Borisy GG (1972) Colcemid inhibition of cell growth and the characterization of a colcemid-binding activity in Saccharomyces cerevisiae. J Cell Biol 55(2):355–367

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hari M, Wang YQ, Veeraraghavan S, Cabral F (2003) Mutations in alpha- and beta-tubulin that stabilize microtubules and confer resistance to colcemid and vinblastine. Mol Cancer Ther 2(7):597–605

    CAS  PubMed  Google Scholar 

  • Hari M, Loganzo F, Annable T, Tan XZ, Musto S, Morilla DB, Nettles JH et al (2006) Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of beta-tubulin (AsP(26)Glu) and less stable microtubules. Mol Cancer Ther 5(2):270–278. doi:10.1158/1535-7163.MCT-05-0190

    CAS  PubMed  Google Scholar 

  • Hart JW, Sabnis DD (1976) Colchicine binding activity in extracts of higher plants. J Exp Bot 27(6):1353–1360. doi:10.1093/jxb/27.6.1353

    CAS  Google Scholar 

  • Havens CG, Bryant N, Asher L, Lamoreaux L, Perfetto S, Brendle JJ, Werbovetz KA (2000) Cellular effects of leishmanial tubulin inhibitors on L. donovani. Mol Biochem Parasitol 110(2):223–236. doi:10.1016/S0166-6851(00)00272-3

    CAS  PubMed  Google Scholar 

  • Heinig U, Scholz S, Jennewein S (2013) Getting to the bottom of Taxol biosynthesis by fungi. Fungal Divers 60(1):161–170. doi:10.1007/s13225-013-0228-7

    Google Scholar 

  • Hess FD, Bayer DE (1977) Binding of the herbicide trifluralin to Chlamydomonas flagellar tubulin. J Cell Sci 24(1):351–360

    CAS  PubMed  Google Scholar 

  • Hillmann G, Ruthmann A (1982) Effect of mitotic inhibitors on the ultrastructure of root meristem cells. Planta 155(2):124–132. doi:10.1007/BF00392542

    CAS  PubMed  Google Scholar 

  • Hirata Y, Uemura D (1986) Halichondrins—antitumor polyether macrolides from a marine sponge. Pure Appl Chem 58(5):701–710. doi:10.1351/pac198658050701

    CAS  Google Scholar 

  • Hopwood DA (2007) How do antibiotic-producing bacteria ensure their self-resistance before antibiotic biosynthesis incapacitates them? Mol Microbiol 63(4):937–940. doi:10.1111/j.1365-2958.2006.05584.x

    CAS  PubMed  Google Scholar 

  • Hua XQH, Genini D, Gussio R, Tawatao R, Shih H, Kipps TJ, Carson DA et al (2001) Biochemical genetic analysis of indanocine resistance in human leukemia. Cancer Res 61(19):7248–7254

    CAS  PubMed  Google Scholar 

  • Huzil JT, Ludueña RF, Tuszynski J (2006) Comparative modelling of human β tubulin isotypes and implications for drug binding. Nanotechnology 17(4):S90–S100. doi:10.1088/0957-4484/17/4/014

    CAS  Google Scholar 

  • Jordan MA (2002) Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem Anti-Cancer Agents 2(1):1–17

    CAS  Google Scholar 

  • Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4(4):253–265. doi:10.1038/nrc1317

    CAS  PubMed  Google Scholar 

  • Jordan MA, Thrower D, Wilson L (1992) Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J Cell Sci 102:401–416

    CAS  PubMed  Google Scholar 

  • Jordan MA, Toso RJ, Thrower D, Wilson L (1993) Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci U S A 90(20):9552–9556

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kapoor P, Sachdeva M, Madhubala R (1999) Effect of the microtubule stabilising agent taxol on leishmanial protozoan parasites in vitro. FEMS Microbiol Lett 176(2):429–435

    CAS  PubMed  Google Scholar 

  • Kingston DGI (2009) Tubulin-interactive natural products as anticancer agents. J Nat Prod 72(3):507–515. doi:10.1021/np800568j

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kiso T, Fujita K-I, Ping X, Tanaka T, Taniguchi M (2004) Screening for microtubule-disrupting antifungal agents by using a mitotic-arrest mutant of Aspergillus nidulans and novel action of phenylalanine derivatives accompanying tubulin loss. Antimicrob Agents Chemother 48(5):1739–1748. doi:10.1128/AAC.48.5.1739-1748.2004

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kobayashi I, Kobayashi Y, Hardham AR (1997) Inhibition of rust-induced hypersensitive response in flax cells by the microtubule inhibitor oryzalin. Aust J Plant Physiol 24(6):733–740

    CAS  Google Scholar 

  • Komlodi-Pasztor E (2011) Mitosis is not a key target of microtubule agents in patient tumors. Nat Rev Clin Oncol 8(4):244–250

    CAS  PubMed  Google Scholar 

  • Kovács P, Csaba G (2006) Effect of drugs affecting microtubular assembly on microtubules, phospholipid synthesis and physiological indices (signalling, growth, motility and phagocytosis) in Tetrahymena pyriformis. Cell Biochem Funct 24(5):419–429. doi:10.1002/cbf.1238

    PubMed  Google Scholar 

  • Kramers MR, Stebbings H (1977) The insensitivity of Vinca rosea to vinblastine. Chromosoma 61(3):277–287

    CAS  PubMed  Google Scholar 

  • Leandro-García LJ, Leskelä S, Landa I, Montero-Conde C, López-Jiménez E, Letón R, Cascón A et al (2010) Tumoral and tissue-specific expression of the major human beta-tubulin isotypes. Cytoskeleton Hoboken NJ 67(4):214–223. doi:10.1002/cm.20436

    Google Scholar 

  • Lee V, Huang B (1990) Missense mutations at lysine-350 in beta-2-tubulin confer altered sensitivity to microtubule inhibitors in Chlamydomonas. Plant Cell 2(11):1051–1057

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lefèvre J, Chernov KG, Joshi V, Delga S, Toma F, Pastré D, Curmi PA et al (2011) The C terminus of tubulin, a versatile partner for cationic molecules: binding of Tau, polyamines, and calcium. J Biol Chem 286(4):3065–3078. doi:10.1074/jbc.M110.144089

    PubMed Central  PubMed  Google Scholar 

  • Levan A (1940) The effect of acenaphthene and colchicine on mitosis of Allium and Colchicum. Hereditas 26(3–4):262–276. doi:10.1111/j.1601-5223.1940.tb03236.x

    CAS  Google Scholar 

  • Liebmann JE, Cook JA, Lipschultz C, Teague D, Fisher J, Mitchell JB (1993) Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines. Br J Cancer 68(6):1104–1109

    CAS  PubMed Central  PubMed  Google Scholar 

  • Little M, Seehaus T (1988) Comparative analysis of tubulin sequences. Comp Biochem Physiol B Comp Biochem 90(4):655–670. doi:10.1016/0305-0491(88)90320-3

    CAS  Google Scholar 

  • Little M, Ludueña RF, Langford GM, Asnes CF, Farrell K (1981) Comparison of proteolytic cleavage patterns of α-tubulins and β-tubulins from taxonomically distant species. J Mol Biol 149(1):95–107. doi:10.1016/0022-2836(81)90262-X

    CAS  PubMed  Google Scholar 

  • Little M, Ludueña RF, Keenan R, Asnes CF (1982) Tubulin evolution: two major types of α-tubulin. J Mol Evol 19(1):80–86. doi:10.1007/BF02100226

    CAS  PubMed  Google Scholar 

  • Little M, Luduena R, Morejohn L, Asnes C, Hoffman E (1984) The tubulins of animals, plants, fungi and protists implications for metazoan evolution. Orig Life Evol Biosph 13(3–4):169–176. doi:10.1007/BF00927168

    CAS  Google Scholar 

  • Lopes R, Eleutério CV, Gonçalves LMD, Cruz MEM, Almeida AJ (2012) Lipid nanoparticles containing oryzalin for the treatment of leishmaniasis. Eur J Pharm Sci Off J Eur Fed Pharm Sci 45(4):442–450. doi:10.1016/j.ejps.2011.09.017

    CAS  Google Scholar 

  • Löwe J, Li H, Downing KH, Nogales E (2001) Refined structure of alpha beta-tubulin at 3.5 A resolution. J Mol Biol 313(5):1045–1057. doi:10.1006/jmbi.2001.5077

    PubMed  Google Scholar 

  • Ludueña RF (2013) Chapter Two—A hypothesis on the origin and evolution of tubulin. In: Kwang W. Jeon (ed) Int. Rev. Cell Mol. Biol. Academic Press, pp 41–185

  • Luis L, Serrano ML, Hidalgo M, Mendoza-León A (2013) Comparative analyses of the β-tubulin gene and molecular modeling reveal molecular insight into the colchicine resistance in kinetoplastids organisms. BioMed Res Int. doi: 10.1155/2013/843748

  • Lyons-Abbott S, Sackett DL, Wloga D, Gaertig J, Morgan RE, Werbovetz KA, Morrissette NS (2010) α-Tubulin mutations alter oryzalin affinity and microtubule assembly properties to confer dinitroaniline resistance. Eukaryot Cell 9(12):1825–1834. doi:10.1128/EC.00140-10

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mahoney BP, Raghunand N, Baggett B, Gillies RJ (2003) Tumor acidity, ion trapping and chemotherapeutics. I. Acid pH affects the distribution of chemotherapeutic agents in vitro. Biochem Pharmacol 66(7):1207–1218

    CAS  PubMed  Google Scholar 

  • Mallory-Smith CA (2003) Revised classification of herbicides by site of action for weed resistance management strategies. Weed Technol 17(3):605–617

    CAS  Google Scholar 

  • Merlini VV, Nogarol LR, Marin-Morales MA, Fontanetti CS (2012) Toxicity of trifluralin herbicide in a representative of the edaphic fauna: histopathology of the midgut of Rhinocricus padbergi (Diplopoda). Microsc Res Technol 75(10):1361–1369. doi:10.1002/jemt.22075

    CAS  Google Scholar 

  • Mitchison TJ (2012) The proliferation rate paradox in antimitotic chemotherapy. Mol Biol Cell 23(1):1–6. doi:10.1091/mbc.E10-04-0335

    CAS  PubMed Central  PubMed  Google Scholar 

  • Molè Bajer J, Bajer AS (1983) Action of taxol on mitosis: modification of microtubule arrangements and function of the mitotic spindle in Haemanthus endosperm. J Cell Biol 96(2):527–540. doi:10.1083/jcb.96.2.527

    PubMed  Google Scholar 

  • Morejohn LC, Fosket DE (1984) Taxol-induced rose microtubule polymerization in vitro and its inhibition by colchicine. J Cell Biol 99(1 Pt 1):141–147

    CAS  PubMed  Google Scholar 

  • Morejohn LC, Fosket DE (1991) The biochemistry of compounds with anti-microtubule activity in plant cells. Pharmacol Ther 51(2):217–230. doi:10.1016/0163-7258(91)90078-Z

    CAS  PubMed  Google Scholar 

  • Morrissette NS, Mitra A, Sept D, Sibley LD (2004) Dinitroanilines bind α-tubulin to disrupt microtubules. Mol Biol Cell 15(4):1960–1968. doi:10.1091/mbc.E03-07-0530

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mu JH, Bollon AP, Sidhu RS (1999) Analysis of beta-tubulin cDNAs from taxol-resistant Pestalotiopsis microspora and taxol-sensitive Pythium ultimum and comparison of the taxol-binding properties of their products. Mol Gen Genet 262(4–5):857–868

    CAS  PubMed  Google Scholar 

  • Ngan VK, Bellman K, Panda D, Hill BT, Jordan MA, Wilson L (2000) Novel actions of the antitumor drugs vinflunine and vinorelbine on microtubules. Cancer Res 60(18):5045–5051

    CAS  PubMed  Google Scholar 

  • Nogales E, Wolf SG, Downing KH (1998) Structure of the alpha beta tubulin dimer by electron crystallography. Nature 391(6663):199–203. doi:10.1038/34465

    CAS  PubMed  Google Scholar 

  • Nuki G (2008) Colchicine: its mechanism of action and efficacy in crystal-induced inflammation. Curr Rheumatol Rep 10(3):218–227

    CAS  PubMed  Google Scholar 

  • Nyporko AY, Blume YB (2009) Spatial distribution of tubulin mutations conferring resistance to antimicrotubular compounds. In: Blume YB, Baird WV, Yemets AI, Breviario D (eds) Plant cytoskelet. Key tool agro-biotechnol. Springer, Netherlands, pp 397–417

    Google Scholar 

  • Nyporko AY, Yemets AI, Brytsun VN, Lozinsky MO, Blume YB (2009) Structural and biological characterization of the tubulin interaction with dinitroanilines. Cytol Genet 43(4):267–282. doi:10.3103/S0095452709040082

    Google Scholar 

  • Pettit GR, Kamano Y, Fujii Y, Herald CL, Inoue M, Brown P, Gust D et al (1981) Marine animal biosynthetic constituents for cancer chemotherapy. J Nat Prod 44(4):482–485

    CAS  PubMed  Google Scholar 

  • Pettit GR, Singh SB, Hamel E, Lin CM, Alberts DS, Garcia-Kendall D (1989) Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia 45(2):209–211

    CAS  PubMed  Google Scholar 

  • Poleksić V, Karan V (1999) Effects of trifluralin on carp: biochemical and histological evaluation. Ecotoxicol Environ Saf 43(2):213–221. doi:10.1006/eesa.1999.1790

    PubMed  Google Scholar 

  • Quinlan RA, Roobol A, Pogson CI, Gull K (1981) A correlation between in vivo and in vitro effects of the microtubule inhibitors colchicine, parbendazole and nocodazole on myxamoebae of Physarum polycephalum. J Gen Microbiol 122(1):1–6

    CAS  PubMed  Google Scholar 

  • Radchuk VV (2009) The transcriptome of the tubulin gene family in plants. In: Blume YB, Baird WV, Yemets AI, Breviario D (eds) Plant cytoskelet. Key tool agro-biotechnol. Springer Netherlands, Dordrecht, pp 219–241

    Google Scholar 

  • Ravelli RBG, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M (2004) Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428(6979):198–202. doi:10.1038/nature02393

    CAS  PubMed  Google Scholar 

  • Rodi DJ, Janes RW, Sanganee HJ, Holton RA, Wallace B, Makowski L (1999) Screening of a library of phage-displayed peptides identifies human Bcl-2 as a taxol-binding protein. J Mol Biol 285(1):197–203. doi:10.1006/jmbi.1998.2303

    CAS  PubMed  Google Scholar 

  • Rosenbaum JL, Carlson K (1969) Cilia regeneration in Tetrahymena and its inhibition by colchicine. J Cell Biol 40(2):415–425. doi:10.1083/jcb.40.2.415

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schmit AC, Lambert AM (1988) Plant actin filament and microtubule interactions during anaphase–telophase transition: effects of antagonist drugs. Biol Cell Auspices Eur Cell Biol Organ 64(3):309–319

    CAS  Google Scholar 

  • Sharma S, Poliks B, Chiauzzi C, Ravindra R, Blanden AR, Bane S (2010) Characterization of the colchicine binding site on avian tubulin isotype βVI. Biochemistry (Mosc) 49(13):2932–2942. doi:10.1021/bi100159p

    CAS  Google Scholar 

  • Shitan N, Yazaki K (2007) Accumulation and membrane transport of plant alkaloids. Curr Pharm Biotechnol 8(4):244–252

    CAS  PubMed  Google Scholar 

  • Siddiqi SH, Marwat KB (1983) Cytomorphological effects of colchicine on wheat (Triticum aestivum). Pak J Agric Res 4(2):120–125

    Google Scholar 

  • Sipkema D, Franssen MCR, Osinga R, Tramper J, Wijffels RH (2005) Marine sponges as pharmacy. Mar Biotechnol N Y N 7(3):142–162. doi:10.1007/s10126-004-0405-5

    CAS  Google Scholar 

  • Staniek A, Woerdenbag HJ, Kayser O (2009) Taxomyces andreanae: a presumed paclitaxel producer demystified? Planta Med 75(15):1561–1566. doi:10.1055/s-0029-1186181

    CAS  PubMed  Google Scholar 

  • Stanton RA, Gernert KM, Nettles JH, Aneja R (2011) Drugs that target dynamic microtubules: a new molecular perspective. Med Res Rev 31(3):443–481. doi:10.1002/med.20242

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260(5105):214–216

    CAS  PubMed  Google Scholar 

  • Stokkermans TJ, Schwartzman JD, Keenan K, Morrissette NS, Tilney LG, Roos DS (1996) Inhibition of Toxoplasma gondii replication by dinitroaniline herbicides. Exp Parasitol 84(3):355–370. doi:10.1006/expr.1996.0124

    CAS  PubMed  Google Scholar 

  • Talpir R, Benayahu Y, Kashman Y, Pannell L, Schleyer M (1994) Hemiasterlin and geodiamolide TA: two new cytotoxic peptides from the marine sponge Hemiasterella minor (Kirkpatrick). Tetrahedron Lett 35(25):4453–4456. doi:10.1016/S0040-4039(00)73382-X

    CAS  Google Scholar 

  • Ter Haar E, Rosenkranz HS, Hamel E, Day BW (1996) Computational and molecular modeling evaluation of the structural basis for tubulin polymerization inhibition by colchicine site agents. Bioorg Med Chem 4(10):1659–1671

    PubMed  Google Scholar 

  • Thomas TRA, Kavlekar DP, LokaBharathi PA (2010) Marine drugs from sponge–microbe association—a review. Mar Drugs 8(4):1417–1468. doi:10.3390/md8041417

    CAS  PubMed Central  PubMed  Google Scholar 

  • Traub-Cseko YM, Ramalho-Ortigão JM, Dantas AP, de Castro SL, Barbosa HS, Downing KH (2001) Dinitroaniline herbicides against protozoan parasites: the case of Trypanosoma cruzi. Trends Parasitol 17(3):136–141. doi:10.1016/S1471-4922(00)01834-1

    CAS  PubMed  Google Scholar 

  • Tuszynski JA, Craddock TJA, Mane JY, Barakat K, Tseng C-Y, Gajewski M, Winter P et al (2012) Modeling the yew tree tubulin and a comparison of its interaction with paclitaxel to human tubulin. Pharm Res 29(11):3007–3021. doi:10.1007/s11095-012-0829-y

    CAS  PubMed  Google Scholar 

  • Utkhede RS (1982) Effects of six herbicides on the growth of Phytophthora cactorum and a bacterial antagonist. Pestic Sci 13(6):693–695. doi:10.1002/ps.2780130617

    CAS  Google Scholar 

  • Vaughn K, Lehnen L (1991) Mitotic disrupter herbicides. Weed Sci 39(3):450–457

    CAS  Google Scholar 

  • Vaughn K, Vaughan M (1988) Mitotic disrupters from higher plants—effects on plant cells. Acs Symp Ser 380:273–293

    CAS  Google Scholar 

  • Vaughn KC, Marks MD, Weeks DP (1987) A dinitroaniline-resistant mutant of Eleusine indica exhibits cross-resistance and supersensitivity to antimicrotubule herbicides and drugs. Plant Physiol 83(4):956–964

    CAS  PubMed Central  PubMed  Google Scholar 

  • Verdier-Pinard P, Pasquier E, Xiao H, Burd B, Villard C, Lafitte D, Miller LM et al (2009) Tubulin proteomics: towards breaking the code. Anal Biochem 384(2):197–206. doi:10.1016/j.ab.2008.09.020

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wagner LJ (1994) Effect of taxol and related compounds on growth of plant pathogenic fungi. Phytopathology 84:1173–1178

    CAS  Google Scholar 

  • Walker GE, Morey BG (1999) Effects of chemicals and microbial antagonists on nematodes and fungal pathogens of citrus roots. Aust J Exp Agric 39(5):629–637

    Google Scholar 

  • Wasteneys GO (2002) Microtubule organization in the green kingdom: chaos or self-order? J Cell Sci 115(7):1345–1354

    CAS  PubMed  Google Scholar 

  • Waters AL, Hill RT, Place AR, Hamann MT (2010) The expanding role of marine microbes in pharmaceutical development. Curr Opin Biotechnol 21(6):780–786. doi:10.1016/j.copbio.2010.09.013

    CAS  PubMed Central  PubMed  Google Scholar 

  • Werbovetz KA, Brendle JJ, Sackett DL (1999) Purification, characterization, and drug susceptibility of tubulin from Leishmania. Mol Biochem Parasitol 98(1):53–65

    CAS  PubMed  Google Scholar 

  • Williams NE, Williams RJ (1976) Macronuclear division with and without microtubules in Tetrahymena. J Cell Sci 20(1):61–77

    CAS  PubMed  Google Scholar 

  • Wloga D, Gaertig J (2010) Post-translational modifications of microtubules. J Cell Sci 123(20):3447–3455. doi:10.1242/jcs.063727

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yamamoto E, Zeng LH, Baird WV (1998) Alpha-tubulin missense mutations correlate with antimicrotubule drug resistance in Eleusine indica. Plant Cell 10(2):297–308. doi:10.1105/tpc.10.2.297

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yemets AI, Blume YB (2008) Progress in plant polyploidization based on antimicrotubular drugs. Open Hortic J 1:15–20

    CAS  Google Scholar 

Download references

Acknowledgments

This work was partially supported by project UNCE204013. We would like to thank Dr. Vladimír Hampl, Dr. Marian Novotný, and Dr. Marie Macůrková for their helpful comments.

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Libusová.

Additional information

Handling Editor: Peter Nick

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 404 kb)

ESM 2

(PDF 276 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dostál, V., Libusová, L. Microtubule drugs: action, selectivity, and resistance across the kingdoms of life. Protoplasma 251, 991–1005 (2014). https://doi.org/10.1007/s00709-014-0633-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00709-014-0633-0

Keywords

Navigation