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Cited by 140Cell death mechanisms and regulationMicrotubule and mitosis dynamicsCancer-related Molecular Pathways

Mitotic Catastrophe Results in Cell Death by Caspase-Dependentand Caspase-Independent Mechanisms

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Mansilla, Sylvia, Priebe, Waldemar, Portugal, José·2006·Cell Cycle
DOI 10.4161/cc.5.1.2267
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Abstract

Exposure of MDA-MB-231 and MCF-7/VP human breast carcinoma cells to the anthracyclines doxorubicin and WP631 induced polyploidy, formation of multinucleated cells and cell death by mitotic catastrophe through caspase-dependent and caspase-independent mechanisms. In both cell lines, the antiproliferative effect of WP631 was higher than that of doxorubicin and a transient halt in G(2)/M was observed without cell senescence, while p53-dependent apoptosis did not occur in these cells. Mitotic catastrophe was linked to necrosis, but also to apoptosis-like death, estimated by differential cell staining with annexin-V-fluorescein and propidium iodide. Drug-induced changes in the expression of c-myc and p21(WAF1), and in their respective protein levels, were observed. They depended on the cell line, the anthracycline used and its concentration, and they were consistent with the cell cycle progression through G(2) to mitosis. Significant activation of caspase-2 and caspase-3 was only observed in MDA-MB-231 cells treated with doxorubicin but not with WP631, indicating that caspases may be not mandatory for the occurrence of cell death through mitotic catastrophe. In MCF-7/VP cells, which do not express functional caspase-3, mitotic catastrophe was also induced.

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Cited by 140

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Authors
Mansilla, S., Priebe, W., & Portugal, J.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • The University of Texas MD Anderson Cancer Center (US)
ORCID
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2005-11-15
Volume
5
Issue
1
Pages
53-60
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.4161/cc.5.1.2267
OpenAlex
W2033408779
Cited by
140
References
0
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 9 · 2013: 12 · 2012: 8
FWCI
3.90
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Welch Foundation
  • Generalitat de Catalunya
  • Ministerio de Ciencia y Tecnología
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
mitotic catastrophe, anthracyclines, doxorubicin, breast cancer cells, MDA-MB-231 cells, polyploidy, multinucleated cells, caspase-independent cell death, caspase-2, caspase-3, necrosis, apoptosis-like death, c-Myc, p21, G2/M cell cycle arrest, p53-independent apoptosis
MeSH terms
Daunorubicin, Doxorubicin, Enzyme Activation, Humans, Mitosis, Propidium, Gene Expression Regulation, Neoplastic, Cell Death, Caspases, Cell Line, Tumor

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