ArticleMolecular carcinogenesis2012
Pharmacological inhibition of Mdm2 triggers growth arrest and promotes DNA breakage in mouse colon tumors and human colon cancer cells.
Article in Molecular carcinogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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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
23 citing papers in PubMed, 45 citations in OpenAlex.
- Exploring the therapeutic role of carnosol in cancer: from molecular insights to clinical promise.Medical oncology (Northwood, London, England) · 2025Review
- RBM47 functions as an anti-oncogene by regulating expression and alternative splicing of cell proliferation and apoptosis associated genes in colorectal cancer cells.Scientific reports · 2025Article
- MDM2: current research status and prospects of tumor treatment.Cancer cell international · 2024Review
- Article
- Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review.World journal of gastrointestinal surgery · 2023Review
- Therapeutics Targeting p53-MDM2 Interaction to Induce Cancer Cell Death.International journal of molecular sciences · 2022Review
- Roles of DANCR/microRNA-518a-3p/MDMA ceRNA network in the growth and malignant behaviors of colon cancer cells.BMC cancer · 2020Article
- Cisplatin in Combination with MDM2 Inhibition Downregulates Rad51 Recombinase in a Bimodal Manner to Inhibit Homologous Recombination and Augment Tumor Cell Kill.Molecular pharmacology · 2020Article
- Article
- CMIP Promotes Proliferation and Metastasis in Human Glioma.BioMed research international · 2017Article
- The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression.Cold Spring Harbor perspectives in medicine · 2016Review
- Article
- ARTIK-52 induces replication-dependent DNA damage and p53 activation exclusively in cells of prostate and breast cancer origin.Cell cycle (Georgetown, Tex.) · 2016Article
- Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic effects of Wee1 inhibitors.Oncotarget · 2015Article
- P53 mutations in colorectal cancer - molecular pathogenesis and pharmacological reactivation.World journal of gastroenterology · 2015Review
- p53 and NF-κB coregulate proinflammatory gene responses in human macrophages.Cancer research · 2014Article
- DRAGO (KIAA0247), a new DNA damage-responsive, p53-inducible gene that cooperates with p53 as oncosuppressor. [Corrected].Journal of the National Cancer Institute · 2014Article
- Drugging the p53 pathway: understanding the route to clinical efficacy.Nature reviews. Drug discovery · 2014Review
- Novel piperazine-based compounds inhibit microtubule dynamics and sensitize colon cancer cells to tumor necrosis factor-induced apoptosis.The Journal of biological chemistry · 2014Article
- Identification of novel compounds that enhance colon cancer cell sensitivity to inflammatory apoptotic ligands.Cancer biology & therapy · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The p53 tumor suppressor protein performs a number of cellular functions, ranging from the induction of cell cycle arrest and apoptosis to effects on DNA repair. Modulating p53 activity with Mdm2 inhibitors is a promising approach for treating cancer; however, it is presently unclear how the in vivo application of Mdm2 inhibitors impact the myriad processes orchestrated by p53. Since approximately half of all colon cancers (predominately cancers with microsatellite instability) are p53-normal, we assessed the anticancer activity of the Mdm2 inhibitor Nutlin-3 in the mouse azoxymethane (AOM) colon cancer model, in which p53 remains wild type. Using a cell line derived from an AOM-induced tumor, we found that four daily exposures to Nutlin-3 induced persistent p53 stabilization and cell cycle arrest without significant apoptosis. A 4-day dosing schedule in vivo generated a similar response in colon tumors; growth arrest without significantly increased apoptosis. In adjacent normal colon tissue, Nutlin-3 treatment reduced both cell proliferation and apoptosis. Surprisingly, Nutlin-3 induced a transient DNA damage response in tumors but not in adjacent normal tissue. Nutlin-3 likewise induced a transient DNA damage response in human colon cancer cells in a p53-dependent manner, and enhanced DNA strand breakage and cell death induced by doxorubicin. Our findings indicate that Mdm2 inhibitors not only trigger growth arrest, but may also stimulate p53's reported ability to slow homologous recombination repair. The potential impact of Nutlin-3 on DNA repair in tumors suggests that Mdm2 inhibitors may significantly accentuate the tumoricidal actions of certain therapeutic modalities.
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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.