ArticleCell death discovery2025
Dual role of p21 in regulating apoptosis and mitotic integrity in response to doxorubicin in colon cancer cells.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- The p53-Associated Regulation of ATF4 mRNA Expression Involves p21 and p130 in a Stress-Dependent Manner.Cells · 2026Article
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- Arctigenin Suppresses Breast Cancer Growth In Vitro and In Vivo Through Subtype-Specific Multi-Targeting Activity.International journal of molecular sciences · 2026Article
- Construction of a risk scoring model based on machine learning and validation of the role of the key gene SERPINE1 in the progression of colon cancer.Cancer cell international · 2026Article
- BRD4-mediated transcriptional activation of PDLIM4 enhances p21 stability and chemosensitivity in lung adenocarcinoma independent of p53.BMC biology · 2026Article
- Investigating the Molecular Mechanisms of the Anticancer Effects of Eugenol and Cinnamaldehyde Against Colorectal Cancer (CRC) Cells In Vitro.International journal of molecular sciences · 2026Article
- Article
- Integrated Multi-Omics Analysis and Cross-Model Validation Reveal Mitochondrial Signatures in Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Article
- Pioneering biomimetic biomaterial for leukemia therapy enhancement: a review.Frontiers in bioengineering and biotechnology · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
This study explores the multifaceted role of p21 in mediating cellular responses to DNA-damaging agents, with a focus on doxorubicin treatment in HCT116 colon carcinoma cells. We investigated how different doses of doxorubicin affect cells with varied p21 and p53 statuses, revealing distinct roles for p21 depending on the drug dosage. At high doses (HD), p21 is more critical than p53 in mediating apoptosis, whereas at low doses (LD), p21 is essential for preventing mitotic defects and multinucleation. Notably, reintroducing p21 or pharmacologically inhibiting CDK1 reduced multinucleation. The absence of p21 upon LD doxorubicin exposure led to aberrant chromosome segregation, persistent DNA damage response (DDR) activation, and increased non-homologous end-joining (NHEJ) activity, resulting in unrepaired DNA accumulation and multinucleation. Additionally, mitotic defects in p21-deficient cells were associated with mislocalization of key mitotic regulators, Aurora B and mitotic kinesin-like protein 1 (MKLP1), exacerbating defective mitosis. In summary, p21 functions as a dual regulator in response to DNA damage, promoting apoptosis at HD and preventing mitotic failure at LD. These insights have significant implications for cancer therapy, highlighting the potential of targeting the p21 to enhance treatment efficacy.
Identifiers
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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.