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Cited by 1,095Microtubule and mitosis dynamicsCancer Treatment and PharmacologySynthesis and biological activity

Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations.

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Jordan, M A, Toso, R J, Thrower, D, Wilson, L·1993·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.90.20.9552PMC PMC47607
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Abstract

Taxol inhibited HeLa cell proliferation by inducing a sustained mitotic block at the metaphase/anaphase boundary. Half-maximal inhibition of cell proliferation occurred at 8 nM taxol, and mitosis was half-maximally blocked at 8 nM taxol. Inhibition of mitosis was associated with formation of an incomplete metaphase plate of chromosomes and an altered arrangement of spindle microtubules that strongly resembled the abnormal organization that occurs with low concentrations of vinblastine and other antimitotic compounds. No increase in microtubule polymer mass occurred below 10 nM taxol. The mass of microtubules increased half-maximally at 80 nM taxol and attained maximal levels (5 times normal) at 330 nM taxol. At submicromolar concentrations, taxol suppressed growing and shortening at the ends of microtubules reassembled in vitro from bovine brain tubulin in a manner that resembled suppression by vinblastine. Taxol was concentrated in HeLa cells several hundredfold to levels that were similar to those which suppressed dynamic instability in vitro. The results indicate that taxol shares a common antiproliferative mechanism with vinblastine. At its lowest effective concentrations, taxol appears to block mitosis by kinetically stabilizing spindle microtubules and not by changing the mass of polymerized microtubules.

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  • Taxanes kill cancer cells by binding to and stabilizing β-tubulin on the inner surface of microtubules, increasing their polymerization.

    “Taxanes, such as paclitaxel and docetaxel, kill cancer cells by binding to and stabilizing β-tubulin on the inner surface of microtubules, increasing their polymerization (Jordan et al., 1993).”

    From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Jordan et al., 1993

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Authors
Jordan, M. A., Toso, R. J., Thrower, D., & Wilson, L.
Affiliations
University of California, Santa Barbara (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1993-10-15
Volume
90
Issue
20
Pages
9552-9556
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.90.20.9552
PMC
PMC47607
OpenAlex
W1976033985
Cited by
1,095
References
27
Citations by year
2026: 19 · 2025: 18 · 2024: 17 · 2023: 28 · 2022: 28 · 2021: 32 · 2020: 31 · 2019: 32 · 2018: 27 · 2017: 45 · 2016: 30 · 2015: 24 · 2014: 44 · 2013: 40 · 2012: 40
FWCI
9.43
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Cancer Society
  • National Cancer Institute (R01CA057291, CA57291-01)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
Keywords
paclitaxel, mitotic arrest, cell proliferation inhibition, HeLa cells, spindle microtubules, microtubule stabilization, microtubule dynamic instability, vinblastine, tubulin, antimitotic agents
MeSH terms
Cell Division, Dose-Response Relationship, Drug, Fluorescent Antibody Technique, HeLa Cells, Humans, Microtubules, Mitosis, Spindle Apparatus, Polymers, Paclitaxel, In Vitro Techniques

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