Cited by 384Microtubule and mitosis dynamicsCancer Treatment and PharmacologyHeterocyclic Compound Synthesis and Bioactivity

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Taxanes: Microtubule and Centrosome Targets, and Cell Cycle Dependent Mechanisms of Action

Abal, M., Andreu, J., Barasoain, I.·2003·Current Cancer Drug Targets

DOI 10.2174/1568009033481967

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Abstract

Microtubules are highly dynamic cellular polymers made of alphabeta-tubulin and associated proteins. They play a key role during mitosis, participating in the exact organization and function of the spindle, and are critical for assuring the integrity of the segregated DNA. Therefore, they represent one of the more effective targets in current cancer therapy. Paclitaxel (Taxol) is the prototype of the taxane family of antitumor drugs, and it was the first natural product shown to stabilize microtubules. This unique mechanism of action is in contrast to other microtubule poisons, such as Vinca alkaloids, colchicine, and cryptophycines, which inhibit tubulin polymerization. Taxanes block cell cycle progression through centrosomal impairment, induction of abnormal spindles and suppression of spindle microtubule dynamics. Triggering of apoptosis by aberrant mitosis or by subsequent multinucleated G1-like state related to mitotic slippage, depends on cell type and drug schedule. The development of fluorescent derivatives of paclitaxel led us to locate spindle pole microtubules and centrosomes as main sub-cellular targets of cytotoxic taxoids in living cells. In this review we discuss these findings in the context of a cell cycle-dependent response to taxanes, based on the cellular targets, and the status of the implicated cell cycle checkpoints. We also review those events that can influence this response, like the different signal transduction pathways activated/inactivated in relation to Bcl-2 phosphorylation and induction of apoptosis, and the controversial role of the p53 status on cell sensitivity to paclitaxel. Finally, cell cycle-dependent resistance, an emerging concept in combination sequential chemotherapy, is discussed on the basis of the cell cycle-dependent mechanisms of action of taxanes.

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Authors: Abal, M., Andreu, J., & Barasoain, I.
Affiliations: Centre National de la Recherche Scientifique (FR)
ORCID: Abal, M.
Andreu, J.
Venue: Current Cancer Drug Targets
Publisher: Bentham Science Publishers Ltd.
Published: 2003-06-01
Volume: 3
Issue: 3
Pages: 193-203
ISSN: 1568-0096 (ISSN-L)
DOI: 10.2174/1568009033481967
OpenAlex: W2164778107
Cited by: 383
References: 0
Citations by year: 2026: 7 · 2025: 14 · 2024: 18 · 2023: 21 · 2022: 22 · 2021: 22 · 2020: 14 · 2019: 19 · 2018: 22 · 2017: 21 · 2016: 23 · 2015: 11 · 2014: 22 · 2013: 14 · 2012: 16
FWCI: 5.35
Type: journal article
Language: en
Open access: closed
Locations: Current Cancer Drug Targets (publishedVersion)
PubMed (publishedVersion)
DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Funders: Fundación Científica Asociación Española Contra el Cáncer
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 › Heterocyclic Compound Synthesis and Bioactivity
Keywords: taxanes, paclitaxel, microtubules, centrosome, spindle microtubules, mitosis, mitotic slippage, apoptosis, Bcl-2 phosphorylation, p53, taxane resistance, cell cycle checkpoints, antimitotic agents
MeSH terms: Animals, Cell Cycle, Humans, Microtubules, Drug Delivery Systems, Paclitaxel, Centrosome

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Taxanes: Microtubule and Centrosome Targets, and Cell Cycle Dependent Mechanisms of Action

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