ArticleBritish journal of cancer2013
Nutlin-3 preferentially sensitises wild-type p53-expressing cancer cells to DR5-selective TRAIL over rhTRAIL.
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
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- p53 stabilisation potentiates [European journal of nuclear medicine and molecular imaging · 2024Article
- Semi-supervised analysis of myeloid and T cell behavior iniScience · 2023Article
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- Repressed miR-34a Expression Dictates the Cell Fate to Corneal Endothelium Failure.Investigative ophthalmology & visual science · 2022Article
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- Dying to Survive-The p53 Paradox.Cancers · 2021Review
- Genome-scale CRISPR screening identifies cell cycle and protein ubiquitination processes as druggable targets for erlotinib-resistant lung cancer.Molecular oncology · 2021Article
- Functional roles of E3 ubiquitin ligases in gastric cancer.Oncology letters · 2020Review
- Ceramide-Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations.Molecular cancer therapeutics · 2020Article
- Helping the Released Guardian: Drug Combinations for Supporting the Anticancer Activity of HDM2 (MDM2) Antagonists.Cancers · 2019Review
- Death receptor 5 is activated by fucosylation in colon cancer cells.The FEBS journal · 2019Article
- RMP/URI inhibits both intrinsic and extrinsic apoptosis through different signaling pathways.International journal of biological sciences · 2019Article
- Impact of p53 status on TRAIL-mediated apoptotic and non-apoptotic signaling in cancer cells.PloS one · 2019Article
- Construction and characterization of a new TRAIL soluble form, active at picomolar concentrations.Oncotarget · 2018Article
- Miltirone-induced apoptosis in cisplatin-resistant lung cancer cells through upregulation of p53 signaling pathways.Oncology letters · 2018Article
- Impact of RUNX2 on drug-resistant human pancreatic cancer cells with p53 mutations.BMC cancer · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumour cell-selective activation of apoptosis by recombinant human TNF-related apoptosis-inducing ligand (rhTRAIL) is enhanced through co-activation of p53 by chemotherapeutic drugs. The novel anticancer agent nutlin-3 provides a promising alternative for p53 activation by disrupting the interaction between p53 and its negative feedback regulator MDM2.
methodsWe examined whether nutlin-3 enhances apoptosis induction by rhTRAIL and the DR5-selective TRAIL variant D269H/E195R in wild-type p53-expressing ovarian, colon and lung cancer cell lines and in an ex vivo model of human ovarian cancer.
resultsNutlin-3 enhanced p53, p21, MDM2 and DR5 surface expression. Although nutlin-3 did not induce apoptosis, it preferentially enhanced D269H/E195R-induced apoptosis over rhTRAIL. Combination treatment potentiated the cleavage of caspases 8, 9, 3 and PARP. P53 and MDM2 siRNA experiments showed that this enhanced apoptotic effect was mediated by wild-type p53. Indeed, nutlin-3 did not enhance rhTRAIL-induced apoptosis in OVCAR-3 cells harbouring mutant p53. Addition of the chemotherapeutic drug cisplatin to the combination further increased p53 and DR5 levels and rhTRAIL- and D269H/E195R-induced apoptosis. As a proof of concept, we show that the combination of D269H/E195R, nutlin-3 and cisplatin induced massive apoptosis in ex vivo tissue slices of primary human ovarian cancers.
conclusionNutlin-3 is a potent enhancer of D269H/E195R-induced apoptosis in wild-type p53-expressing cancer cells. Addition of DNA-damaging agents such as cisplatin further enhances DR5-mediated apoptosis.
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