ArticleFrontiers in pharmacology2025
MDM2 inhibitor induces apoptosis in colon cancer cells through activation of the CHOP-DR5 pathway, independent of p53 phenotype.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
3 citing papers in PubMed.
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- Engineered bacteria as exogenous organelle mimics restore PTEN and p53 tumor suppressor functions for cancer therapy.Nature communications · 2026Article
- Systemic Inflammation and Survival in Stage IV Colorectal Cancer: A Retrospective Cohort Study.Journal of clinical medicine · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Murine double minute 2 (MDM2), a key negative regulator of p53, forms a feedback loop with p53 to drive tumor progression, including colorectal cancer. Nutlin-3a, an MDM2 inhibitor, induces apoptosis in wild-type p53 tumors, but its effects on p53-mutated cancers and potential p53-independent apoptotic mechanisms remain unclear. Methods: We investigated Nutlin-3a's effects on colon cancer cells with varying p53 phenotypes. Endoplasmic reticulum (ER) stress-associated CHOP was detected and knocked down to explore mechanisms. In vitro and in vivo experiments assessed Nutlin-3a's synergy with 5-fluorouracil and TRAIL. Results: Nutlin-3a activated caspase-8-dependent extrinsic apoptosis in colon cancer cells via DR5 upregulation, independent of p53 status. ER stress and CHOP activation mediated DR5 induction, driven by calcium release. Combined Nutlin-3a treatment enhanced sensitivity to 5-fluorouracil and TRAIL Discussion: These findings reveal a novel p53-independent apoptotic mechanism of Nutlin-3a involving ER stress and death receptor signaling. This pathway highlights Nutlin-3a's potential as an adjuvant therapy for colon cancer, even in p53-mutated tumors, by enhancing chemotherapeutic efficacy through extrinsic apoptosis.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.