ArticleCell cycle (Georgetown, Tex.)2014
Post-slippage multinucleation renders cytotoxic variation in anti-mitotic drugs that target the microtubules or mitotic spindle.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 59 citations in OpenAlex.
- The Persistent Power of the Taxane/Platin Chemotherapy.Cancers · 2025Review
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- Effects of Vinorelbine on M2 Macrophages in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Article
- The Second Selectivity of Taxanes to Malignant Cells --- Nuclear Envelope Malleability.Journal of Cancer · 2025Article
- Cancer nuclear envelope rupture and repair in taxane resistance.Medical review (2021) · 2024Review
- Beyond Death: Unmasking the Intricacies of Apoptosis Escape.Molecular diagnosis & therapy · 2024Review
- Article
- Imaging Flow Cytometry of Multi-Nuclearity.Methods in molecular biology (Clifton, N.J.) · 2023Article
- G2/M arrest and mitotic slippage induced by fenbendazole in canine melanoma cells.Veterinary medicine and science · 2022Article
- The Role of the APC/C and Its Coactivators Cdh1 and Cdc20 in Cancer Development and Therapy.Frontiers in genetics · 2022Review
- Rationale for combination of paclitaxel and CDK4/6 inhibitor in ovarian cancer therapy - non-mitotic mechanisms of paclitaxel.Frontiers in oncology · 2022Review
- Role of Senescence in Tumorigenesis and Anticancer Therapy.Journal of oncology · 2022Review
- Rac1/ROCK-driven membrane dynamics promote natural killer cell cytotoxicity via granzyme-induced necroptosis.BMC biology · 2021Article
- Targeting the actin/tropomyosin cytoskeleton in epithelial ovarian cancer reveals multiple mechanisms of synergy with anti-microtubule agents.British journal of cancer · 2021Article
- Multinucleation associated DNA damage blocks proliferation in p53-compromised cells.Communications biology · 2021Article
- Breaking malignant nuclei as a non-mitotic mechanism of taxol/paclitaxel.Journal of cancer biology · 2021Article
- Review
- LIN9 and NEK2 Are Core Regulators of Mitotic Fidelity That Can Be Therapeutically Targeted to Overcome Taxane Resistance.Cancer research · 2020Article
- Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics.Cell death & disease · 2019Article
- Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule-targeting agents by blocking cytokinesis.Cancer science · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One common cancer chemotherapeutic strategy is to perturb cell division with anti-mitotic drugs. Paclitaxel, the classic microtubule-targeting anti-mitotic drug, so far still outperforms the newer, more spindle-specific anti-mitotics in the clinic, but the underlying cellular mechanism is poorly understood. In this study we identified post-slippage multinucleation, which triggered extensive DNA damage and apoptosis after drug-induced mitotic slippage, contributes to the extra cytotoxicity of paclitaxel in comparison to the spindle-targeting drug, Kinesin-5 inhibitor. Based on quantitative single-cell microscopy assays, we showed that attenuation of the degree of post-slippage multinucleation significantly reduced DNA damage and apoptosis in response to paclitaxel, and that post-slippage apoptosis was likely mediated by the p53-dependent DNA damage response pathway. Paclitaxel appeared to act as a double-edge sword, capable of killing proliferating cancer cells both during mitotic arrest and after mitotic slippage by inducing DNA damage. Our results thus suggest that to predict drug response to paclitaxel and anti-mitotics in general, 2 distinct sets of bio-markers, which regulate mitotic and post-slippage cytotoxicity, respectively, may need to be considered. Our findings provide important new insight not only for elucidating the cytotoxic mechanisms of paclitaxel, but also for understanding the variable efficacy of different anti-mitotic chemotherapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.