ArticleCell death and differentiation2011
A novel microtubule-modulating noscapinoid triggers apoptosis by inducing spindle multipolarity via centrosome amplification and declustering.
Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 67 citations in OpenAlex.
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- Targeting YES1 Disrupts Mitotic Fidelity and Potentiates the Response to Taxanes in Triple-Negative Breast Cancer.Cancer research · 2024Article
- Thiostrepton induces spindle abnormalities and enhances Taxol cytotoxicity in MDA-MB-231 cells.Molecular biology reports · 2024Article
- Terminally differentiated osteoclasts organize centrosomes into large clusters for microtubule nucleation and bone resorption.Molecular biology of the cell · 2022Article
- Centrosome Aberrations as Drivers of Chromosomal Instability in Breast Cancer.Endocrinology · 2021Review
- Down-Regulating HAUS6 Suppresses Cell Proliferation by Activating the p53/p21 Pathway in Colorectal Cancer.Frontiers in cell and developmental biology · 2021Article
- Arsenic trioxide disturbs the LIS1/NDEL1/dynein microtubule dynamic complex by disrupting the CLIP170 zinc finger in head and neck cancer.Toxicology and applied pharmacology · 2020Article
- Review
- The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling.Oxidative medicine and cellular longevity · 2020Article
- YLT-11, a novel PLK4 inhibitor, inhibits human breast cancer growth via inducing maladjusted centriole duplication and mitotic defect.Cell death & disease · 2018Article
- Clinically Applicable Inhibitors Impacting Genome Stability.Molecules (Basel, Switzerland) · 2018Review
- Inhibition of cancer progression by a novel trans-stilbene derivative through disruption of microtubule dynamics, driving G2/M arrest, and p53-dependent apoptosis.Cell death & disease · 2018Article
- Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells.The Journal of cell biology · 2018Article
- Article
- The more the messier: centrosome amplification as a novel biomarker for personalized treatment of colorectal cancers.Journal of biomedical research · 2016Review
- A FRET biosensor reveals spatiotemporal activation and functions of aurora kinase A in living cells.Nature communications · 2016Article
- Centrosome amplification, chromosomal instability and cancer: mechanistic, clinical and therapeutic issues.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2016Review
- Paclitaxel and the dietary flavonoid fisetin: a synergistic combination that induces mitotic catastrophe and autophagic cell death in A549 non-small cell lung cancer cells.Cancer cell international · 2016Article
- Centrosome-declustering drugs mediate a two-pronged attack on interphase and mitosis in supercentrosomal cancer cells.Cell death & disease · 2014Article
- Novel 9'-substituted-noscapines: synthesis with Suzuki cross-coupling, structure elucidation and biological evaluation.European journal of medicinal chemistry · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
We have previously shown that a non-toxic noscapinoid, EM011 binds tubulin without altering its monomer/polymer ratio. EM011 is more active than the parent molecule, noscapine, in inducing G2/M arrest, inhibiting cellular proliferation and tumor growth in various human xenograft models. However, the mechanisms of mitotic-block and subsequent cell death have remained elusive. Here, we show that EM011-induced attenuation of microtubule dynamics was associated with impaired association of microtubule plus-end tracking proteins, such as EB1 and CLIP-170. EM011 treatment then led to the formation of multipolar spindles containing 'real' centrioles indicating drug-induced centrosome amplification and persistent centrosome declustering. Centrosome amplification was accompanied by an upregulation of Aurora A and Plk4 protein levels, as well as a surge in the kinase activity of Aurora A, suggesting a deregulation of the centrosome duplication cycle. Cell-cycle phase-specific experiments showed that the 'cytotoxicity-window' of the drug encompasses the late S-G2 period. Drug-treatment, excluding S-phase, not only resulted in lower sub-G1 population but also attenuated centrosome amplification and spindle multipolarity, suggesting that drug-induced centrosome amplification is essential for maximal cell death. Subsequent to a robust mitotic arrest, EM011-treated cells displayed diverse cellular fates suggesting a high degree of intraline variation. Some 'apoptosis-evasive' cells underwent aberrant cytokinesis to generate rampant aneuploidy that perhaps contributed to drug-induced cell death. These data indicate that spindle multipolarity induction by means of centrosome amplification has an exciting chemotherapeutic potential that merits further investigation.
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Registered trials
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.