Seminars in Oncology
Volume 35 , Pages S6-S12 , June 2008

Exploring the Mechanisms of Action of the Novel Microtubule Inhibitor Vinflunine

  • Mary Ann Jordan

      Affiliations

    • University of California-Santa Barbara, Santa Barbara, CA.
    • Corresponding Author InformationAddress correspondence to Mary Ann Jordan, PhD, Department of Molecular, Cellular & Developmental Biology, Mail Code 9610, University of California-Santa Barbara, Santa Barbara, CA 93106
  • ,
  • Susan Band Horwitz

      Affiliations

    • Albert Einstein College of Medicine, Bronx, NY.
  • ,
  • Sharon Lobert

      Affiliations

    • University of Mississippi Medical Center, Jackson, MS.
  • ,
  • John J. Correia

      Affiliations

    • University of Mississippi Medical Center, Jackson, MS.

References 

  1. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P, et al. Macromolecules: Structure, Shape, and Information. In: Molecular biology of the cell. 4th ed.. Oxford, UK: Garland Publishing; 2002;p. 89–138
  2. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4:253–265
  3. Verdier-Pinard P, Wang F, Burd B, Angeletti RH, Horwitz SB, Orr GA. Direct analysis of tubulin expression in cancer cell lines by electrospray ionization mass spectrometry. Biochemistry. 2003;42:12019–12027
  4. Cassimeris L. The oncoprotein 18/stathmin family of microtubule destabilizers. Curr Opin Cell Biol. 2002;14:18–24
  5. Giodini A, Kallio MJ, Wall NR, Gorbsky GJ, Toqnin S, Marchisio PC, et al. Regulation of microtubule stability and mitotic progression by survivin. Cancer Res. 2002;62:2462–2467
  6. Maney T, Wagenbach M, Wordeman L. Molecular dissection of the microtubule depolymerizing activity of mitotic centromere-associated kinesin. J Biol Chem. 2001;276:34753–34758
  7. Spittle C, Charrasse S, Larroque C, Cassimeris L. The interaction of TOGp with microtubules and tubulin. J Biol Chem. 2000;275:20748–20753
  8. Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol. 1997;13:83–117
  9. McNally FJ. Modulation of microtubule dynamics during the cell cycle. Curr Opin Cell Biol. 1996;8:23–29
  10. Nogales E. Structural insight into microtubule function. Annu Rev Biophys Biomol Struct. 2001;30:397–420
  11. Chen W, Zhang D. Kinetochore fibre dynamics outside the context of the spindle during anaphase. Nat Cell Biol. 2004;6:227–231
  12. Mitchison TJ. Polewards microtubule flux in the mitotic spindle: Evidence from photoactivation of fluorescence. J Cell Biol. 1989;109:637–652
  13. Wilson PJ, Forer A. Effects of nanomolar taxol on crane-fly spermatocyte spindles indicate that acetylation of kinetochore microtubules can be used as a marker of poleward tubulin flux. Cell Motil Cytoskeleton. 1997;37:20–32
  14. Hayden JH, Bowser SS, Rieder CL. Kinetochores capture astral microtubules during chromosome attachment to the mitotic spindle: direct visualization in live newt lung cells. J Cell Biol. 1990;111:1039–1045
  15. Li X, Nicklas RB. Mitotic forces control a cell-cycle checkpoint. Nature. 1995;373:630–632
  16. Mitchison T, Kirschner M. Dynamic instability of microtubule growth. Nature. 1984;312:237–242
  17. Margolis RL, Wilson L. Microtubule treadmilling: What goes around comes around. Bioessays. 1998;20:830–836
  18. Walker RA, O'Brien ET, Pryer NK, et al. Dynamic instability of individual microtubules analyzed by video light microscopy: rate constants and transition frequencies. J Cell Biol. 1988;107:1437–1448
  19. Rodionov VI, Borisy GG. Microtubule treadmilling in vivo. Science. 1997;275:215–218
  20. Waters JC, Mitchison TJ, Rieder CL, Salmon ED. The kinetochore microtubule minus-end disassembly associated with poleward flux produces a force that can do work. Mol Biol Cell. 1996;7:1547–1558
  21. Waterman-Storer CM, Salmon ED. Microtubule dynamics: Treadmilling comes around again. Curr Biol. 1997;7:R369–R372
  22. Jordan MA. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem Anticancer Agents. 2002;2:1–17
  23. Correia JJ, Lobert S. Physiochemical aspects of tubulin-interacting antimitotic drugs. Curr Pharm Des. 2001;7:1213–1228
  24. Compton DA. Spindle assembly in animal cells. Annu Rev Biochem. 2000;69:95–114
  25. Gardner RD, Burke DJ. The spindle checkpoint: Two transitions, two pathways. Trends Cell Biol. 2000;10:154–158
  26. Jordan MA, Toso RJ, Thrower D, Wilson L. Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci U S A. 1993;90:9552–9556
  27. Jordan MA, Wendell K, Gardiner S, Derry WB, Copp H, Wilson L. Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res. 1996;56:816–825
  28. Johnson IS, Armstrong JG, Gorman M, Burnett JP. The vinca alkaloids: A new class of oncolytic agents. Cancer Res. 1963;23:1390–1427
  29. Na GC, Timasheff SN. Thermodynamic linkage between tubulin self-association and the binding of vinblastine. Biochemistry. 1980;19:1355–1365
  30. Lobert S, Correia JJ. Energetics of vinca alkaloid interactions with tubulin. Methods Enzymol. 2000;323:77–103
  31. Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumor agents (VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia). J Am Chem Soc. 1971;93:2325–2327
  32. Nogales E, Wolf SG, Khan IA, Luduena RF, Downing KH. Structure of tubulin at 6.5 A and location of the taxol-binding site. Nature. 1995;375:424–427
  33. Horwitz SB. Taxol (paclitaxel): Mechanisms of action. Ann Oncol. 1994;5(Suppl 6):S3–S6
  34. Derry WB, Wilson L, Jordan MA. Substoichiometric binding of taxol suppresses microtubule dynamics. Biochemistry. 1995;34:2203–2211
  35. Yvon AM, Wadsworth P, Jordan MA. Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol Biol Cell. 1999;10:947–959
  36. Fahy J, Duflos A, Ribet JP, et al. Vinca alkaloids in superacidic media: A method for creating a new family of antitumor derivatives. J Am Chem Soc. 1997;119:8576–8577
  37. Jacquesy JC, Fahy J. Cancer: superacid generation of new antitumor agents. In:  Torrence PF editors. Biomedical chemistry; applying chemical principles to the understanding and treatment of disease. New York, NY: Wiley-Interscience; 2000;p. 227–246
  38. Kruczynski A, Colpaert F, Tarayre JP, Mouillard P, Fahy J, Hill BT. Preclinical in vivo antitumor activity of vinflunine, a novel fluorinated Vinca alkaloid. Cancer Chemother Pharmacol. 1998;41:437–447
  39. Hill BT, Fiebig HH, Waud WR, Poupon MF, Colpaert F, Kruczynski A. Superior in vivo experimental antitumour activity of vinflunine, relative to vinorelbine, in a panel of human tumour xenografts. Eur J Cancer. 1999;35:512–520
  40. Kruczynski A, Barret JM, Etiévant C, Colpaert F, Fahy J, Hill BT. Antimitotic and tubulin-interacting properties of vinflunine, a novel fluorinated Vinca alkaloid. Biochem Pharmacol. 1998;55:635–648
  41. Jean-Decoster C, Brichese L, Barret JM, Tollon Y, Kruczynski A, Hill BT. Vinflunine, a new vinca alkaloid: cytotoxicity, cellular accumulation and action on the interphasic and mitotic microtubule cytoskeleton of PtK2 cells. Anticancer Drugs. 1999;10:537–543
  42. Kruczynski A, Hill BT. Vinflunine, the latest Vinca alkaloid in clinical development (A review of its preclinical anticancer properties). Crit Rev Oncol Hematol. 2001;40:159–173
  43. Okouneva T, Hill BT, Wilson L, Jordan MA. The effects of vinflunine, vinorelbine, and vinblastine on centromere dynamics. Mol Cancer Ther. 2003;2:427–436
  44. Ngan VK, Bellman K, Panda D, Hill BT, Jordan MA, Wilson L. Novel actions of the antitumor drugs vinflunine and vinorelbine on microtubules. Cancer Res. 2000;60:5045–5051
  45. Lobert S, Fahy J, Hill BT, Duflos A, Etievant C, Correia JJ. Vinca alkaloid-induced tubulin spiral formation correlates with cytotoxicity in the leukemic L1210 cell line. Biochemistry. 2000;39:12053–12062
  46. Lobert S, Ingram JW, Hill BT, Correia JJ. A comparison of thermodynamic parameters for vinorelbine- and vinflunine-induced tubulin self-association by sedimentation velocity. Mol Pharmacol. 1998;53:908–915
  47. Ngan VK, Bellman K, Hill BT, Wilson L, Jordan MA. Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine. Mol Pharmacol. 2001;60:225–232
  48. Gidding CE, Kellie SJ, Kamps WA, de Graaf SS. Vincristine revisited. Crit Rev Oncol Hematol. 1999;29:267–287
  49. Sahenk Z, Barohn R, New P, Mendell JR. Taxol neuropathy (Electrodiagnostic and sural nerve biopsy findings). Arch Neurol. 1994;51:726–729
  50. Etiévant C, Barret JM, Kruczynski A, Perrin D, Hill BT. Vinflunine (20′,20′-difluoro-3′,4′-dihydrovinorelbine), a novel Vinca alkaloid, which participates in P-glycoprotein (Pgp)-mediated multidrug resistance in vivo and in vitro. Invest New Drugs. 1998;16:3–17
  51. Etiévant C, Kruczynski A, Barret JM, Tait AS, Kavallaris M, Hill BT. Markedly diminished drug resistance-inducing properties of vinflunine (20′,20′-difluoro-3′,4′-dihydrovinorelbine) relative to vinorelbine, identified in murine and human tumour cells in vivo and in vitro. Cancer Chemother Pharmacol. 2001;48:62–70
  52. Aggarwal A, Kruczynski A, Frankfurter A, Correia JJ, Lobert S. Murine leukemia cell lines are sensitive to vinflunine. Invest New Drugs. 2007 (in press).
  53. Oakley BR. An abundance of tubulins. Trends Cell Biol. 2000;10:537–542
  54. Sharp DJ, Rogers GC, Scholey JM. Microtubule motors in mitosis. Nature. 2000;407:41–47
  55. Luduena RF. Multiple forms of tubulin: different gene products and covalent modifications. Int Rev Cytol. 1998;178:207–275
  56. Verdier-Pinard P, Shahabi S, Wang F, Burd B, Xiao H, Goldberg GL, et al. Detection of human βV-tubulin expression in epithelial cancer cell lines by tubulin proteomics. Biochemistry. 2005;44:15858–15870
  57. Bhattacharya R, Cabral F. A ubiquitous b-tubulin disrupts microtubule assembly and inhibits cell proliferation. Mol Biol Cell. 2004;15:3123–3131
  58. Panda D, Miller HP, Banerjee A, Luduena RF, Wilson L. Microtubule dynamics in vitro are regulated by the tubulin isotype composition. Proc Natl Acad Sci U S A. 1994;91:11358–11362
  59. Derry WB, Wilson L, Khan IA, Luduena RF, Jordan MA. Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified beta-tubulin isotypes. Biochemistry. 1997;36:3554–3562
  60. Kamath K, Wilson L, Cabral F, Jordan MA. βIII-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability. J Biol Chem. 2005;280:12902–12907
  61. Burkhart CA, Kavallaris M, Horwitz SB. The role of beta-tubulin isotypes in resistance to antimitotic drugs. Biochim Biophys Acta. 2001;1471:O1–O9
  62. Banerjee A. Increased levels of tyrosinated alpha-, beta(III)-, and beta(IV)-tubulin isotypes in paclitaxel-resistant MCF-7 breast cancer cells. Biochem Biophys Res Commun. 2002;293:598–601
  63. Sève P, Mackey J, Isaac S, Trédan O, Souquet P-J, Pérol M. Class III β-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel. Mol Cancer Ther. 2005;4:2001–2007
  64. Sève P, Isaac S, Trédan O, Souquet P-J, Pachéco Y, Pérol M. Expression of class III β-tubulin is predictive of patient outcome in patients with non-small cell lung cancer receiving vinorelbine-based chemotherapy. Clin Cancer Res. 2005;11:5481–5486
  65. Bernard-Marty C, Treilleux I, Dumontet C, Cardoso F, Fellows A, Gancberg D. Microtubule-associated parameters as predictive markers of docetaxel activity in advanced breast cancer patients: results of a pilot study. Clin Breast Cancer. 2002;3:341–345

 Dr Jordan has received research support and consulting fees from Bristol-Myers Squibb. Dr Horwitz does not have any financial conflict to report. Dr Lobert has received research support from Pierre Fabre Oncologie and consulting fees from Pierre Fabre Oncologie and Bristol-Myers Squibb. Dr Correia has received research support from Pierre Fabre Oncologie and consulting fees from Pierre Fabre Oncologie, Bristol-Myers Squibb, and Eisai.

PII: S0093-7754(08)00018-3

doi: 10.1053/j.seminoncol.2008.01.009

Seminars in Oncology
Volume 35 , Pages S6-S12 , June 2008