ArticleBritish journal of pharmacology2017
5-fluorouracil causes endothelial cell senescence: potential protective role of glucagon-like peptide 1.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 70 citations in OpenAlex.
- The Relationship Between Immunogenic Cell Death and Cellular Senescence in Cancer Immunotherapy.Life (Basel, Switzerland) · 2026Review
- Mechanisms and therapeutic potential of therapy-induced cellular senescence in radiotherapy- and chemotherapy-related alimentary tract mucositis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Review
- Thymoquinone and pentoxifylline modulate 5-fluorouracil-induced senescence and apoptosis in colorectal cancer spheroids.Research in pharmaceutical sciences · 2026Article
- Article
- Vascular Toxicities of Cancer Therapies: 2025 Update.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- A human 3D culture-organ-on-chip platform for investigating the tumor microenvironment response to ionizing radiation.iScience · 2026Article
- Biological properties of soluble CD146 and its role and mechanisms in disease progression.Frontiers in immunology · 2026Review
- The fat-heart entanglement and the role of 'osteopontin mechanics' in cardiometabolic senescence.European journal of clinical investigation · 2026Review
- Therapy-induced senescence in breast cancer and cardiovascular disease: a double-edged biological process.Frontiers in cardiovascular medicine · 2026Review
- Article
- A CEBPB/TYMP/GDF15 signaling axis mediates tumor growth and cisplatin resistance in bladder cancer.Translational oncology · 2025Article
- Axillary dissection is avoidable in most cT1N0 triple-negative & HER2+ breast cancers treated with upfront surgery.Breast cancer research and treatment · 2025Article
- Article
- Modulating senescence-associated secretory phenotype-driven paracrine effects to overcome therapy -induced senescence: senolytic effects of hesperidin and quercetin in A549 lung adenocarcinoma cells.Molecular biology reports · 2025Article
- KRAS inhibition reverses chemotherapy resistance promoted by therapy-induced senescence-like in pancreatic ductal adenocarcinoma.Translational oncology · 2025Article
- Cisplatin and methotrexate induce brain microvascular endothelial and microglial senescence in mouse models of chemotherapy-associated cognitive impairment.GeroScience · 2025Article
- Persisting blood-brain barrier disruption following cisplatin treatment in a mouse model of chemotherapy-associated cognitive impairment.GeroScience · 2025Article
- Article
- The Potential Role of GLP1-RAs Against Anticancer-Drug Cardiotoxicity: A Scoping Review.Journal of clinical medicine · 2025Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purpose5-fluorouracil (5FU) and its prodrug, capecitabine, can damage endothelial cells, whilst endothelial integrity is preserved by glucagon-like peptide 1 (GLP-1). Here, we studied the effect of 5FU on endothelial senescence and whether GLP-1 antagonizes it. EXPERIMENTAL APPROACH: EA.hy926 cells were exposed to 5FU or sera from patients taking capecitabine, with or without pre-incubation with GLP-1. Senescence was identified by expression of senescence-associated β-galactosidase and p16 KEY
resultsBoth 5FU and sera from capecitabine-treated patients stimulated endothelial cell senescence. 5FU-elicited senescence occurred via activation of p38 and JNK, and was associated with decreased eNOS and SIRT-1 levels. Furthermore, 5FU up-regulated VCAM1 and TYMP (encodes enzyme activating capecitabine and 5FU), and sVCAM-1 and CD146 concentrations were higher after than before capecitabine chemotherapy. A non-significant trend for higher ICAM1 levels was also observed. GLP-1 counteracted 5FU-initiated senescence and reduced eNOS and SIRT-1 expression, this protection being mediated by GLP-1 receptor, ERK1/2 and, possibly, PKA and PI3K. CONCLUSIONS AND IMPLICATIONS: 5FU causes endothelial cell senescence and dysfunction, which may contribute to its cardiovascular side effects. 5FU-triggered senescence was prevented by GLP-1, raising the possibility of using GLP-1 analogues and degradation inhibitors to treat 5FU and capecitabine vascular toxicity. LINKED ARTICLES: This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.