![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 10, Issue 4, 947-959, April 1999
*Molecular and Cellular Biology Program, University of
Massachusetts, Amherst, Massachusetts, 01003; and
Microtubules are intrinsically dynamic polymers, and their dynamics
play a crucial role in mitotic spindle assembly, the mitotic checkpoint, and chromosome movement. We hypothesized that, in living cells, suppression of microtubule dynamics is
responsible for the ability of taxol to inhibit mitotic progression and
cell proliferation. Using quantitative fluorescence video microscopy, we examined the effects of taxol (30-100 nM) on the dynamics of individual microtubules in two living human tumor cell lines: Caov-3 ovarian adenocarcinoma cells and A-498 kidney carcinoma cells. Taxol accumulated more in Caov-3 cells than in A-498 cells. At
equivalent intracellular taxol concentrations, dynamic instability was
inhibited similarly in the two cell lines. Microtubule shortening rates
were inhibited in Caov-3 cells and in A-498 cells by 32 and 26%,
growing rates were inhibited by 24 and 18%, and dynamicity was
inhibited by 31 and 63%, respectively. All mitotic spindles were
abnormal, and many interphase cells became multinucleate (Caov-3, 30%;
A-498, 58%). Taxol blocked cell cycle progress at the
metaphase/anaphase transition and inhibited cell proliferation. The
results indicate that suppression of microtubule dynamics by taxol
deleteriously affects the ability of cancer cells to properly assemble
a mitotic spindle, pass the metaphase/anaphase checkpoint, and produce progeny.
Department of Molecular, Cellular, and Developmental
Biology, University of California, Santa Barbara, California, 93106
Corresponding author. E-mail
address: jordan{at}lifesci.lscf.ucsb.edu.
This article has been cited by other articles:
|
|
 |
|
  H. Chen, J. Yang, P. S. Low, and J.-X. Cheng Cholesterol Level Regulates Endosome Motility via Rab Proteins Biophys. J., February 15, 2008; 94(4): 1508 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Petit, M. A. Karajannis, L. Vincent, L. Young, J. Butler, A. T. Hooper, K. Shido, H. Steller, D. J. Chaplin, E. Feldman, et al. The microtubule-targeting agent CA4P regresses leukemic xenografts by disrupting interaction with vascular cells and mitochondrial-dependent cell death Blood, February 15, 2008; 111(4): 1951 - 1961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Nikonov, H.-P. Hauri, B. Lauring, and G. Kreibich Climp-63-mediated binding of microtubules to the ER affects the lateral mobility of translocon complexes J. Cell Sci., July 1, 2007; 120(13): 2248 - 2258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Choe, Z. Chen, C. M. Klass, X. Zhang, and D. M. Shin Enhancement of Docetaxel-Induced Cytotoxicity by Blocking Epidermal Growth Factor Receptor and Cyclooxygenase-2 Pathways in Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., May 15, 2007; 13(10): 3015 - 3023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Shajahan, A. Wang, M. Decker, R. D. Minshall, M. C. Liu, and R. Clarke Caveolin-1 Tyrosine Phosphorylation Enhances Paclitaxel-mediated Cytotoxicity J. Biol. Chem., February 23, 2007; 282(8): 5934 - 5943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Arasaki, K. Tani, T. Yoshimori, D. J. Stephens, and M. Tagaya Nordihydroguaiaretic Acid Affects Multiple Dynein-Dynactin Functions in Interphase and Mitotic Cells Mol. Pharmacol., February 1, 2007; 71(2): 454 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhao, I. Gaidarov, and J. H. Keen Phosphoinositide 3-Kinase C2{alpha} Links Clathrin to Microtubule-dependent Movement J. Biol. Chem., January 12, 2007; 282(2): 1249 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xiao, P. Verdier-Pinard, N. Fernandez-Fuentes, B. Burd, R. Angeletti, A. Fiser, S. B. Horwitz, and G. A. Orr Inaugural Article: Insights into the mechanism of microtubule stabilization by Taxol PNAS, July 5, 2006; 103(27): 10166 - 10173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Bunker, K. Kamath, L. Wilson, M. A. Jordan, and S. C. Feinstein FTDP-17 Mutations Compromise the Ability of Tau to Regulate Microtubule Dynamics in Cells J. Biol. Chem., April 28, 2006; 281(17): 11856 - 11863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Lee and S. M. Swain Peripheral Neuropathy Induced by Microtubule-Stabilizing Agents J. Clin. Oncol., April 1, 2006; 24(10): 1633 - 1642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Huang, L. Lopez-Barcons, B. S. Freeze, A. B. Smith III, G. L. Goldberg, S. B. Horwitz, and H. M. McDaid Potentiation of Taxol Efficacy by Discodermolide in Ovarian Carcinoma Xenograft-Bearing Mice Clin. Cancer Res., January 1, 2006; 12(1): 298 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. I. Strickland, E. J. Donnelly, and D. R. Burgess Induction of Cytokinesis Is Independent of Precisely Regulated Microtubule Dynamics Mol. Biol. Cell, October 1, 2005; 16(10): 4485 - 4494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Shannon, J. C. Canman, C. B. Moree, J. S. Tirnauer, and E. D. Salmon Taxol-stabilized Microtubules Can Position the Cytokinetic Furrow in Mammalian Cells Mol. Biol. Cell, September 1, 2005; 16(9): 4423 - 4436. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Jordan, K. Kamath, T. Manna, T. Okouneva, H. P. Miller, C. Davis, B. A. Littlefield, and L. Wilson The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth Mol. Cancer Ther., July 1, 2005; 4(7): 1086 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Andorfer, C. M. Acker, Y. Kress, P. R. Hof, K. Duff, and P. Davies Cell-Cycle Reentry and Cell Death in Transgenic Mice Expressing Nonmutant Human Tau Isoforms J. Neurosci., June 1, 2005; 25(22): 5446 - 5454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-P. H. Yang, P. Verdier-Pinard, F. Wang, E. Lippaine-Horvath, L. He, D. Li, G. Hofle, I. Ojima, G. A. Orr, and S. B. Horwitz A highly epothilone B-resistant A549 cell line with mutations in tubulin that confer drug dependence Mol. Cancer Ther., June 1, 2005; 4(6): 987 - 995. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Levy, A. C. LeBoeuf, M. R. Massie, M. A. Jordan, L. Wilson, and S. C. Feinstein Three- and Four-repeat Tau Regulate the Dynamic Instability of Two Distinct Microtubule Subpopulations in Qualitatively Different Manners: IMPLICATIONS FOR NEURODEGENERATION J. Biol. Chem., April 8, 2005; 280(14): 13520 - 13528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kamath, L. Wilson, F. Cabral, and M. A. Jordan {beta}III-Tubulin Induces Paclitaxel Resistance in Association with Reduced Effects on Microtubule Dynamic Instability J. Biol. Chem., April 1, 2005; 280(13): 12902 - 12907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Taraboletti, G. Micheletti, R. Dossi, P. Borsotti, M. Martinelli, F. Fiordaliso, A. J. Ryan, and R. Giavazzi Potential Antagonism of Tubulin-Binding Anticancer Agents in Combination Therapies Clin. Cancer Res., April 1, 2005; 11(7): 2720 - 2726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Pasquier, S. Honore, B. Pourroy, M. A. Jordan, M. Lehmann, C. Briand, and D. Braguer Antiangiogenic Concentrations of Paclitaxel Induce an Increase in Microtubule Dynamics in Endothelial Cells but Not in Cancer Cells Cancer Res., March 15, 2005; 65(6): 2433 - 2440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, A. O'Brate, A. Zelnak, and P. Giannakakou Survivin Deregulation in {beta}-Tubulin Mutant Ovarian Cancer Cells Underlies Their Compromised Mitotic Response to Taxol Cancer Res., December 1, 2004; 64(23): 8708 - 8714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Van Bruaene, G. Joss, and P. Van Oostveldt Reorganization and in Vivo Dynamics of Microtubules during Arabidopsis Root Hair Development Plant Physiology, December 1, 2004; 136(4): 3905 - 3919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Fanara, S. Turner, R. Busch, S. Killion, M. Awada, H. Turner, A. Mahsut, K. L. LaPrade, J. M. Stark, and M. K. Hellerstein In Vivo Measurement of Microtubule Dynamics Using Stable Isotope Labeling with Heavy Water: EFFECT OF TAXANES J. Biol. Chem., November 26, 2004; 279(48): 49940 - 49947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Aspen Cancer Conference Fellows Toxicol Pathol, October 1, 2004; 32(6): 749 - 761. [PDF]
|
|
|
|
|
|
E. Pasquier, M. Carre, B. Pourroy, L. Camoin, O. Rebai, C. Briand, and D. Braguer Antiangiogenic activity of paclitaxel is associated with its cytostatic effect, mediated by the initiation but not completion of a mitochondrial apoptotic signaling pathway Mol. Cancer Ther., October 1, 2004; 3(10): 1301 - 1310. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Honore, K. Kamath, D. Braguer, S. B. Horwitz, L. Wilson, C. Briand, and M. A. Jordan Synergistic Suppression of Microtubule Dynamics by Discodermolide and Paclitaxel in Non-Small Cell Lung Carcinoma Cells Cancer Res., July 15, 2004; 64(14): 4957 - 4964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Lee, M. K. Keutmann, M. L. Dowling, E. Harris, G. Chan, and G. D. Kao Inactivation of the mitotic checkpoint as a determinant of the efficacy of microtubule-targeted drugs in killing human cancer cells Mol. Cancer Ther., June 1, 2004; 3(6): 661 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Bunker, L. Wilson, M. A. Jordan, and S. C. Feinstein Modulation of Microtubule Dynamics by Tau in Living Cells: Implications for Development and Neurodegeneration Mol. Biol. Cell, June 1, 2004; 15(6): 2720 - 2728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Loegering, S. J. H. Arlander, J. Hackbarth, B. T. Vroman, P. Roos-Mattjus, K. M. Hopkins, H. B. Lieberman, L. M. Karnitz, and S. H. Kaufmann Rad9 Protects Cells from Topoisomerase Poison-induced Cell Death J. Biol. Chem., April 30, 2004; 279(18): 18641 - 18647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. D. Baker, M. Zhao, C. K. K. Lee, J. Verweij, Y. Zabelina, J. R. Brahmer, A. C. Wolff, A. Sparreboom, and M. A. Carducci Comparative Pharmacokinetics of Weekly and Every-Three-Weeks Docetaxel Clin. Cancer Res., March 15, 2004; 10(6): 1976 - 1983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Honore, K. Kamath, D. Braguer, L. Wilson, C. Briand, and M. A. Jordan Suppression of microtubule dynamics by discodermolide by a novel mechanism is associated with mitotic arrest and inhibition of tumor cell proliferation Mol. Cancer Ther., December 1, 2003; 2(12): 1303 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-G. Chen, C.-P. H. Yang, M. Cammer, and S. Band Horwitz Gene Expression and Mitotic Exit Induced by Microtubule-Stabilizing Drugs Cancer Res., November 15, 2003; 63(22): 7891 - 7899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Makrides, T. E. Shen, R. Bhatia, B. L. Smith, J. Thimm, R. Lal, and S. C. Feinstein Microtubule-dependent Oligomerization of Tau: IMPLICATIONS FOR PHYSIOLOGICAL TAU FUNCTION AND TAUOPATHIES J. Biol. Chem., August 29, 2003; 278(35): 33298 - 33304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Panda, J. C. Samuel, M. Massie, S. C. Feinstein, and L. Wilson Differential regulation of microtubule dynamics by three- and four-repeat tau: Implications for the onset of neurodegenerative disease PNAS, August 5, 2003; 100(16): 9548 - 9553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kelling, K. Sullivan, L. Wilson, and M. A. Jordan Suppression of Centromere Dynamics by Taxol(R) in Living Osteosarcoma Cells Cancer Res., June 1, 2003; 63(11): 2794 - 2801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Okouneva, B. T. Hill, L. Wilson, and M. A. Jordan The Effects of Vinflunine, Vinorelbine, and Vinblastine on Centromere Dynamics Mol. Cancer Ther., May 1, 2003; 2(5): 427 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Lee and B. Goldstein Mechanisms of cell positioning during C. elegans gastrulation Development, March 2, 2003; 130(2): 307 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Diaz, I. Barasoain, and J. M. Andreu Fast Kinetics of Taxol Binding to Microtubules. EFFECTS OF SOLUTION VARIABLES AND MICROTUBULE-ASSOCIATED PROTEINS J. Biol. Chem., February 28, 2003; 278(10): 8407 - 8419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-L. Yang, J.-X. Pan, L. Sun, and S.-C. J. Yeung p21 Waf-1 (Cip-1) Enhances Apoptosis Induced by Manumycin and Paclitaxel in Anaplastic Thyroid Cancer Cells J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 763 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vantieghem, Y. Xu, Z. Assefa, J. Piette, J. R. Vandenheede, W. Merlevede, P. A. M. de Witte, and P. Agostinis Phosphorylation of Bcl-2 in G2/M Phase-arrested Cells following Photodynamic Therapy with Hypericin Involves a CDK1-mediated Signal and Delays the Onset of Apoptosis J. Biol. Chem., September 27, 2002; 277(40): 37718 - 37731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Rogers, G. C. Rogers, D. J. Sharp, and R. D. Vale Drosophila EB1 is important for proper assembly, dynamics, and positioning of the mitotic spindle J. Cell Biol., September 3, 2002; 158(5): 873 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Giannakakou, M. Nakano, K. C. Nicolaou, A. O'Brate, J. Yu, M. V. Blagosklonny, U. F. Greber, and T. Fojo Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics PNAS, August 6, 2002; 99(16): 10855 - 10860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Landen, R. Lang, S. J. McMahon, N. M. Rusan, A.-M. Yvon, A. W. Adams, M. D. Sorcinelli, R. Campbell, P. Bonaccorsi, J. C. Ansel, et al. Noscapine Alters Microtubule Dynamics in Living Cells and Inhibits the Progression of Melanoma Cancer Res., July 15, 2002; 62(14): 4109 - 4114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Giodini, M. J. Kallio, N. R. Wall, G. J. Gorbsky, S. Tognin, P. C. Marchisio, M. Symons, and D. C. Altieri Regulation of Microtubule Stability and Mitotic Progression by Survivin Cancer Res., May 1, 2002; 62(9): 2462 - 2467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Li, J.-R. Ciu, Y. Ye, J.-M. Min, L.-H. Zhang, K. Wang, M. Gares, J. Cros, M. Wright, and J. Leung-Tack Antitumor activity of Z-ajoene, a natural compound purified from garlic: antimitotic and microtubule-interaction properties Carcinogenesis, April 1, 2002; 23(4): 573 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Kidd, M. F. Pilkington, M. J. Schell, K. E. Fogarty, J. N. Skepper, C. W. Taylor, and P. Thorn Paclitaxel Affects Cytosolic Calcium Signals by Opening the Mitochondrial Permeability Transition Pore J. Biol. Chem., February 15, 2002; 277(8): 6504 - 6510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. W. Dent and K. Kalil Axon Branching Requires Interactions between Dynamic Microtubules and Actin Filaments J. Neurosci., December 15, 2001; 21(24): 9757 - 9769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Bradley, N. L. Webb, F. H. Anthony, P. Devanesan, P. A. Witman, S. Hemamalini, M. C. Chander, S. D. Baker, L. He, S. B. Horwitz, et al. Tumor Targeting by Covalent Conjugation of a Natural Fatty Acid to Paclitaxel Clin. Cancer Res., October 1, 2001; 7(10): 3229 - 3238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Goncalves, D. Braguer, K. Kamath, L. Martello, C. Briand, S. Horwitz, L. Wilson, and M. A. Jordan Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics PNAS, September 13, 2001; (2001) 191388598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-M. C. Yvon, D. J. Gross, and P. Wadsworth Antagonistic forces generated by myosin II and cytoplasmic dynein regulate microtubule turnover, movement, and organization in interphase cells PNAS, June 28, 2001; (2001) 141224198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-P. H. Yang and S. B. Horwitz Taxol Mediates Serine Phosphorylation of the 66-kDa Shc Isoform Cancer Res., September 1, 2000; 60(18): 5171 - 5178. [Abstract] [Full Text]
|
|
|
|
|
|
C. Iancu, S. J. Mistry, S. Arkin, and G. F. Atweh Taxol and Anti-Stathmin Therapy: A Synergistic Combination that Targets the Mitotic Spindle Cancer Res., July 1, 2000; 60(13): 3537 - 3541. [Abstract] [Full Text]
|
|
|
|
|
|
J. F. Diaz, R. Strobe, Y. Engelborghs, A. A. Souto, and J. M. Andreu Molecular Recognition of Taxol by Microtubules. KINETICS AND THERMODYNAMICS OF BINDING OF FLUORESCENT TAXOL DERIVATIVES TO AN EXPOSED SITE J. Biol. Chem., August 18, 2000; 275(34): 26265 - 26276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-M. C. Yvon, D. J. Gross, and P. Wadsworth Antagonistic forces generated by myosin II and cytoplasmic dynein regulate microtubule turnover, movement, and organization in interphase cells PNAS, July 17, 2001; 98(15): 8656 - 8661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Goncalves, D. Braguer, K. Kamath, L. Martello, C. Briand, S. Horwitz, L. Wilson, and M. A. Jordan Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics PNAS, September 25, 2001; 98(20): 11737 - 11742. [Abstract] [Full Text] [PDF]
|
|
